Among tumor-producing viruses there are DNA- and RNA-containing ones. DNA viruses are divided into the following 5 classes.
1. Polyomaviruses - simian virus SV40, mouse polyoma virus and human viruses BK and JC.
2. Papillomaviruses - 16 human papillomaviruses and many animal papillomaviruses.
3. Adenoviruses - 37 human viruses, many animal adenoviruses (for example, 24 monkey viruses and 9 cattle viruses).
4. Herpoviruses – human herpes simplex viruses, human cytomegalovirus, Epstein-Barr virus and oncogenic viruses of primates, horses, chickens, rabbits, frogs.
5. Viruses similar to hepatitis B virus are human hepatitis B virus, North American woodchuck hepatitis, ground squirrel hepatitis and duck hepatitis.
1. Type C viruses are causative agents of leukemia and sarcomas.
2. Type B viruses – mouse mammary gland cancer virus.
3. Type A viruses.
4. Type D viruses - a virus isolated from mammary gland cancer in rhesus monkeys, and a virus isolated from human transplantable cells.
The explanation for the occurrence of cancer by the integration of viral and cellular genomes given by L.A. Zilber, it was clear for DNA viruses. However, his theory encountered great difficulties in the case of oncogenic RNA viruses, since viral RNA cannot be incorporated directly into the cell genome.
There are fundamental differences between DNA and RNA tumor viruses. When cells are infected with DNA-containing viruses, either replication occurs, leading to infection, or integration of genomes occurs, leading to cell transformation. RNA viruses only induce the transformation of a normal cell into a malignant one, i.e. When a cell is infected with such a virus, integration of their genomes should occur.
Only in 1970 did the American scientists G. Temin and Mitsutani and, independently of them, D. Baltimore solve this riddle. They proved the possibility of transferring genetic information from RNA to DNA. This discovery overturned the central dogma of molecular biology that genetic information can only be transferred in the DNA-RNA-protein direction.
It took G. Temin five years to discover the enzyme that transfers information from RNA to DNA - RNA-dependent DNA polymerase. This enzyme was named reverse transcriptase. G. Temin managed not only to obtain DNA fragments complementary to a given RNA chain, but also to prove that DNA copies can be integrated into the DNA of cells and transmitted to offspring.
A group of RNA-containing viruses, in the development cycle of which DNA is synthesized using genomic RNA using reverse transcriptase, which is then integrated into the genome of the host cell, is called retroviruses ( Retroviridae– from REversed TRanscription). The retrovirus family includes the Rous sarcoma, myelocytomatosis, Harvey and Moloney murine sarcoma, avian leukemia, avian reticuloendotheliosis, murine leukemia, human T-cell leukemia, and human immunodeficiency viruses.
DNA and RNA containing tumor viruses implement genetic information differently. A DNA-containing virus integrated into the cell’s genome must be physically “cut out” from the cell’s genome to begin its independent existence, and the cell must lose the virus. For RNA viruses, “excision” is not required—transcription replaces it. This is due to the fact that the RNA formed during transcription from the genetic material of the virus integrated into the DNA of the cell is viral RNA. Therefore, the genome of a cell that has integrated the genes of RNA viruses never loses them.
Viral DNA, integrated into the genome of a eukaryotic host cell, may not manifest itself in any way for many generations. However, when certain conditions viral genes can be activated and cause either viral replication or the transformation of the cell into cancer.
Numerous works carried out in the 1970–1980s. showed that many animal species have genes that are similar, but not identical, to the genes of retroviruses. These animal and human genes are sometimes called endogenous retroviruses (HERVs), or proviruses.
Typically, HERVs are inactive and less oncogenic to the host species than exogenous ones. It is possible that the cancer-causing genes of a number of retroviruses were once fixed in the DNA of the ancestors of the host species, at the early stages of biological evolution. As the entire DNA of a cell was replicated, oncogenes were passed on from generation to generation. Scientists estimate that HERVs appeared in the genome of human ancestors approximately 50 million years ago.
Integration of an exogenous retrovirus into the host genome is not site-specific (random), so its fixation in the genome is subject to fairly strict rules. Since the provirus does not disappear from the genome, is present in all cells of its carrier and spreads throughout the population, its presence should be harmless to the body and, possibly, provide some benefits to its host.
There is evidence of the involvement of HERV in the regulation of gene expression, in embryonic development, in the prevention of infection by related exogenous retroviruses, in immunosuppression and the development of some autoimmune diseases.
It should also be mentioned that there is a theory of the origin of retroviruses from cellular genes. The main role in this process is given to reverse transcriptase, the inclusion of the DNA it creates in the DNA of the cell and the process of recombination (G. Temin).
Tumor viruses are usually species specific, i.e. only affects animals of a certain species. But there are exceptions to every rule. For example, chicken sarcoma virus can infect rats, rabbits, hamsters, monkeys, lizards and even snakes.
A group of scientists led by B.A. Lapina found that the human leukemia virus can cause a similar disease in two species of monkeys. This led to the creation of an experimental model to study all stages of the disease, starting from the very first stages.
Researchers have shown that when a cell is infected with a retrovirus, the synthesis of its DNA occurs in two stages: first, a DNA strand complementary to it is synthesized along the viral RNA strand, then a second DNA strand complementary to it is completed on the latter, and at the same time, degradation of the viral RNA strand occurs.
Oncoviruses can take part in the development of immunological diseases. Thus, when studying lupus erythematosus using the molecular hybridization method, it was shown that the DNA of cells of tissues affected by the disease contains sequences complementary to the RNA of the measles virus and reverse transcriptase. This indicated the expression of oncovirus in the cells of lupus patients.
Based on the data obtained, it was suggested that in the initial stages of the disease there is an interaction between the measles virus and the latent oncovirus. As a result, the oncovirus reverse transcriptase transcribes measles RNA into DNA, which is then integrated into the cell genome. The expression of these additional genes is manifested in the synthesis of specific viral proteins, some of which are integrated into cell membranes and change their properties. These cells become foreign to the body and are attacked by its own immune system.
Oncoviruses can be activated during tissue transplantation. Consider the following example. When crossing two pure lines of mice, offspring are born that are tolerant to tissue transplantation from either parent: all types of tissue, including lymphoid tissue containing immunoactive cells, engraft. However, if the recipient’s immune system is suppressed before lymphoid tissue transplantation, then after transplantation the expression of oncoviruses sharply increases in mice. Over time, animals develop malignant lymphomas.
It is possible that oncoviruses are normal components of the body that take part in the processes of the cell cycle, differentiation and proliferation. Then aging, the action of physical and chemical carcinogens can cause the development of cancer. However, the presence of carcinogens is not typical for the natural habitat, and the disease of individuals beyond the reproductive period cannot affect the fate of the population. At the same time, the oncovirus integrated into the cell genome
"Taming of the Shrew"
During our journey into the microworld you talk about viruses kind words didn't hear. Indeed, they are the enemies of all living things. But is it possible to turn enemies into friends?
The first experiments on “taming” viruses were carried out on phages – “eaters” of bacteria. When they encounter viruses, bacteria “melt” before our eyes. It was this ability of phages that they decided to use to prevent and treat infectious diseases.
But it turned out that in the human body, phages do not kill bacteria as quickly and actively as in a test tube. Moreover, bacteria are not so “stupid” - they quickly become insensitive to the action of phages.
The simplest viruses contain nucleic acid, which acts as the genetic material of both the microorganism itself and its capsid, which is a protein sheath. The composition of some viruses is supplemented with fats and carbohydrates. Viruses lack part of the enzymes that are responsible for reproductive function, so they can reproduce only after entering the cell of a living organism. The metabolism of the infected cell is then adjusted to produce viral components rather than its own. Each cell contains certain genetic information, which, under certain circumstances, can be considered as instructions for the synthesis of a specific type of protein inside the cell. The infected cell perceives this information as a guide to action.
Dimensions
As for the size of DNA and RNA containing viruses, it is in the range of 20-300 nm. Viruses are generally smaller in size than bacteria. Red blood cells, for example, are an order of magnitude larger than viral cells. Capable of infection, a full-fledged infectious viral particle outside a healthy body is called a virion. The virion core contains one or more nucleic acid molecules. The capsid is a protein shell that covers the virion nucleic acid, providing protection from the harmful effects of the environment. The nucleic acid included in the virion is considered the genome of the virus and is expressed in deoxyribonucleic acid, or DNA, and ribonucleic acid (RNA). Unlike bacteria, viruses do not contain a combination of these two types of acid.
Let's consider the main stages of reproduction of DNA-containing viruses.
Reproduction of viruses
To be able to do so, it is necessary to penetrate into the host cells. Some viruses can exist in a wide variety of hosts, while others have a predilection for specific species. At the initial stage of infection, the virus introduces genetic material in the form of DNA or RNA into the cell. Its reproductive function, as well as the further development of cells, directly depend on the activity and production of genes and proteins of the virus.
To produce cells, DNA-containing viruses do not have enough of their own proteins, so similar carrier substances are used. Some time after infection, only a small part of the original viruses remains in the cell. This phase is called the eclipse phase. The genome of the virus closely interacts with the carrier during this period. Then, after several stages, the accumulation of virus progeny begins in the intracellular space. This is called the maturation phase. Let's consider the sequence of stages of reproduction of DNA-containing viruses.
Cycle of life
The life cycle of viruses consists of several stages that are mandatory:
1.Adsorption on a carrier cell. This is the initial and important stage of recognition of target cells by receptors. Adsorption can occur on cells of organs or tissues. The process triggers the mechanism for further integration of the virus into the cell. A certain amount of ions is required to bind cells. This is necessary to reduce electrostatic repulsion. If penetration into the cell fails, the virus looks for a new target for integration and the process repeats. This phenomenon explains the certainty in the routes of entry of the virus into the human body.
For example, the mucous membrane of the upper respiratory tract has receptors for the influenza virus. Skin cells, on the contrary, do not have any. For this reason, it is impossible to become infected with influenza through the skin; this is only possible by inhaling virus particles. Bacterial viruses in the form of filaments or without processes cannot attach to cell walls, so they are adsorbed on fimfibria. At the initial stage, adsorption occurs due to electrostatic interaction. This phase is reversible, since the virus particle is easily separated from the cell chosen as the target. Starting from the second phase, separation is not possible.
2. The next stage of reproduction of DNA-containing viruses is characterized by the entry of the whole virion or nucleic acid secreted by it inside the host cell. The virus integrates into the animal’s body more easily, since the cells in this case are not equipped with a membrane. If the virion has a lipoprotein membrane on the outside, then upon contact it collides with a similar protection of the host cell and the virus enters the cytoplasm. Viruses that penetrate bacteria, plants and fungi are more difficult to integrate, since in this case they are forced to pass through the rigid cell wall. To achieve this, bacteriophages, for example, are equipped with the enzyme lysozyme, which helps dissolve hard cell walls. We will consider examples of DNA viruses below.
3. The third stage is called deproteinization. It is characterized by the release of nucleic acid, which is the carrier of genetic information. In some viruses, for example, bacteriophages, this process is combined with the second stage, since the protein shell of the virion remains outside the host cell. The virion is able to penetrate the cell by capturing the latter. In this case, a vacuole-phagosome appears, which absorbs the primary lysosomes. In this case, cleavage into enzymes occurs only in the protein part of the viral cell, and the nucleic acid remains unchanged. It is this that subsequently significantly reforms the functioning of a healthy cell, forcing it to produce the substances needed by the virus. The virus itself is not provided with the mechanisms necessary for such procedures. There is such a thing as a viral genome strategy, which involves the implementation of genetic information.
4. The fourth stage of reproduction of DNA-containing viruses is accompanied by the production of substances necessary for the life of the virus, which is carried out under the influence of nucleic acid. First, early mRNA is produced, which will become the basis for the proteins of the virus. Early molecules are those that arose before the release of nucleic acid. Molecules that arise after acid replication are called late. It is important to understand that the production of molecules directly depends on the type of nucleic acid of a particular virus. During biosynthesis, DNA-containing viruses adhere to a specific pattern, including specific stages - DNA-RNA-protein. Small viruses use RNA polymerases in the transcription process. Large ones, such as the smallpox virus, are synthesized not in the cell nucleus, but in the cytoplasm.
Groups of RNA viruses
1. The first group has the simplest structure. It includes corona, toga and picornaviruses. Transcription in these types of virus does not occur, since the single-stranded RNA of the virion independently performs the function of a matrix acid, that is, it represents the basis for the production of proteins at the level of cellular ribosomes. Thus, their bioproduction scheme looks like RNA-protein. Viruses of this group are also called positive genomic or plus-strand viruses.
2. The second group of DNA and RNA viruses includes minus-strand viruses, that is, they have a negative genome. These are measles, influenza, mumps viruses and many others. They also contain single-stranded RNA, but it is not suitable for direct translation. For this reason, data is first transferred to the RNA of the virion, and the resulting matrix acid will subsequently serve as the basis for the production of viral proteins. Transcription in this case is determined by ribonucleic acid-dependent RNA polymerase. This enzyme is brought by the virion, since it is initially absent in the cell. This is because the cell does not need to process RNA to produce other RNA. So, the bioproduction scheme in this case will look like RNA-RNA-protein.
3. The third group consists of the so-called retroviruses. They are also included in the category of oncoviruses. Their biosynthesis occurs along a more complex path. In the initial single-stranded type, at the initial stage, DNA production occurs, which is a unique phenomenon, which has no analogues in nature. The process is controlled by a special enzyme, namely RNA-dependent DNA polymerase. This enzyme is also called reverse transcriptase or reverse transcriptase. The DNA molecule obtained as a result of biosynthesis takes the form of a ring and is designated as a provirus. Next, the molecule is introduced into the cells of the carrier’s chromosomes and transcribed several times by RNA polymerase. The created copies perform the following actions: they represent an RNA matrix, with the help of which the viral protein is produced, as well as the RNA virion. The synthesis scheme is presented as follows: RNA-DNA-RNA-protein.
4. The fourth group is formed from viruses whose RNA has a double-stranded form. Their transcription is carried out by the viral enzyme RNA-dependent RNA polymerase.
5. In the fifth group the production of the components of the virus particle, namely capsid proteins and nucleic acid, occurs repeatedly.
6. The sixth group includes virions, which arise as a result of self-assembly based on multiple copies of proteins and acid. For this purpose, the concentration of virions must reach a critical value. In this case, the components of the virus particle are produced separately from each other in different areas of the cell. Complex viruses also create a protective shell from substances included in the plasma cell membrane.
7. At the final stage, new virus particles are released from the host cell. This process occurs in different ways depending on the type of virus. Some cells then die as cell lysis is released. In other options, budding from the cell is possible, however, this method does not prevent its further death, since the plasma membrane is damaged.
The period until the virus leaves the cell is called latent. The duration of this period can range from several hours to a couple of days.
Genomic viruses containing DNA
1. Genomes such as adeno-, papova- and herpesviruses are transferred and copied in the host cell nucleus. containing double-stranded DNA. Capsids, having entered the cell, are transferred to the membrane of the cell nucleus, so that later, under the influence of certain factors, the DNA of the virus passes into the nucleoplasm and accumulates there. Viruses use the RNA matrix and cellular enzymes of the carrier. A proteins are transferred first, followed by b proteins and g proteins. The RNA template arises from a-22 and a-47. implements DNA transfer, which multiplies according to the rolling ring principle. The capsid, in turn, arises from the g-5 protein. What other DNA virus genomes exist?
2. Poxyviruses are included in the second group. At the initial stage, actions take place in the cytoplasm. There, nucleotides are released and transcription begins. An RNA template is then formed. During the early stages of production, DNA polymerase and about 70 proteins are created, and double-stranded DNA is broken down by the polymerase. On both sides of the genome, replication begins in those places where at the initial stage the unwinding and splitting of DNA chains took place.
3. The third group includes parvoviruses. Reproduction occurs in the cell nucleus of the host and depends on the functions of the cell. In this case, the DNA forms a so-called hairpin structure and acts as a primer. The first 125 base pairs are transferred from the initial strand to the adjacent one, which serves as a template. Thus, an inversion occurs. For synthesis, DNA polymerase is needed, due to which the viral genome is transcribed.
8. The fourth group includes hepadnaviruses. This includes the DNA-containing hepatitis virus. The circular DNA of the virus works as the basis for the production of viral mRNA and plus-strand RNA. This, in turn, becomes the template for the synthesis of the minus strand of DNA.
Fighting methods
As a rule, antibodies aimed at combating certain viruses are produced as a result of the invasion of harmful microorganisms into the host system. However, you can enhance the production of antibodies in advance by getting a preventive vaccination.
Types of vaccination
There are several main types of vaccinations, including:
1. Introduction of weakened virus cells into the body. This provokes the production of an increased amount of antibodies, which makes it possible to fight the normal viral strain.
2. Introduction of an already dead virus. The principle of operation is similar to the first option.
3. Passive immunization. This method involves the introduction of already synthesized antibodies. This can be the blood of a person who has had the disease against which the vaccine is being given, or of an animal, for example, horses. We examined the reproduction sequence of DNA-containing viruses.
To avoid infecting the body with various types of viruses that are dangerous to human health, the body should be protected from potential contact with pathogenic microorganisms. It is quite possible to avoid toxoplasma, mycoplasma, herpes, chlamydia and other common forms of the virus simply by following certain recommendations. This especially applies to children under 15 years of age.
If the child’s body has not been infected with the above strains of viruses, then during adolescence he develops a healthy and strengthened immune system. The main danger of viruses is not always in how they are expressed, but in the impact they have on the protective properties of our body. Examples of DNA and RNA viruses are of interest to many.
The herpes virus, which is present in the body of 9 out of 10 inhabitants of the Earth, reduces immune properties by about 10 percent throughout life, although it may not manifest itself in any way.
Conclusion
In addition to this, which is sometimes not limited only to herpes, the conditions of modern life are far from ideal, which also affects the body’s protective barriers. This point includes the forced urban rhythm of life, poor ecology, unhealthy diet, etc. Against the background of a decrease in a person’s general health, his body becomes less resistant to various viruses and, accordingly, frequent diseases.
Family Picornaviridae (Picornaviridae) consists of 8 genera:
Enteroviruses(polio)
Rhinoviruses(ARVI)
Afthoviruses(foot and mouth disease)
Hepatoviruses(hepatitis A)
This family belongs to non-enveloped viruses containing single-stranded plus RNA. The diameter of the virus is about 30 nm, the virion consists of an icosahedral capsid surrounding single-stranded RNA with the VPg protein. The capsid consists of 12 pentagons (pentamers), each of which in turn consists of 5 protein subunits-protomers: VP1, VP2, VP3, VP4.
Family Reoviruses (Reoviridae) contains 4 genera:
Orthoviruses(gastrointestinal and respiratory infections)
Arboviruses(arboviral infections: Kemerovo virus is transmitted by ticks, sheep blue tongue virus is transmitted by woodlice)
Coltiviruses(Colorado tick fever virus)
Rotaviruses(diarrhea)
The reovirus virion has a spherical shape (diameter 70-85 nm), a two-layer capsid of the icosahedral type, no shell. The genome is represented by double-stranded fragmented (10-12 segments) linear RNA. The inner capsid and genomic RNA make up the core of the virion. The internal capsid of reoviruses contains a transcription system: proteins lambda-1, lambda-3, mu-2. Spines, represented by the lambda-2 protein, extend from the core. In rotaviruses, the internal capsid includes proteins VP1, VP2, VP3, VP6. The outer capsid of reoviruses consists of proteins sigma - 1, sigma - 3, mu - 1c, as well as proteins lambda -2, protruding in the form of spikes. The sigma -1 protein is a hemagglutinin and attachment protein, the mu -1c protein has the ability to infect intestinal cells and subsequently affect the central nervous system.
Family Bunyaviruses (Bunyaviridae) includes 5 genera:
Bunyaviruses(California encephalitis, Jamestown Canyon encephalitis, La Crosse encephalitis, Tyaginya, Inco, Guaroa fevers - viruses are carried by mosquitoes, the incidence is endemic in 20 US states)
Phleboviruses(mosquito fever or pappataci fever). The reservoir and carrier of the virus are female mosquitoes. The disease occurs in Europe (Mediterranean), Asia (Iran, Pakistan), North Africa, Italy, Portugal. Outbreaks occurred in Transcaucasia, Crimea, Moldova and Central Asia.
Neuroviruses(Crimea-Congo hemorrhagic fever, the main reservoir of the virus in nature is many types of pasture ticks, infection occurs through tick suction. In Russia, this disease occurs in the Krasnodar, Stavropol territories, Astrakhan, Volgograd and Rostov regions, the republics of Dagestan, Kalmykia and Karachay- Circassia.
Hantaviruses(HFRS-hemorrhagic fever with renal syndrome)
Tospoviruses non-pathogenic for humans and affects plants
Virions are oval or spherical in shape, with a diameter of 80-120 nm. These are complex RNA genomic viruses containing three internal nucleocapsids with a helical type of symmetry. Each nucleocapsid consists of a nucleocapsid protein N, single-stranded minus RNA, and a transcriptase enzyme. The three RNA segments associated with the nucleocapsid are designated by size: L (long) - large, M (medium) - medium, S (short) - small. The core of the virion is surrounded by a lipoprotein shell, on the surface of which there are spikes - glycoproteins G1 and G2, which are encoded by the M-segment of RNA. w80-
Family Togaviruses (Togaviridae) consists of 4 genera, 2 of which play a role in human pathology:
Alphavirus(viruses transmitted by arthropods cause diseases in humans accompanied by fever, skin rashes, the development of encephalitis and arthritis, in the Primorsky Territory - Semliki forest fever virus)
Rubivirus(rubella virus)
Their genome consists of a linear single-stranded plus RNA surrounded by a capsid (C-protein) with cubic symmetry and consisting of 32 capsomers. The nucleocapsid is surrounded by an outer two-layer lipoprotein shell, on the surface of which glycoproteins E1, E2, E3 are located, penetrating the lipid layer. The diameter of virions is from 65 to 70 nm.
Family Flaviviruses (Flaviviridae) comes from the Latin flavus - yellow, after the name of the disease yellow fever. Pathogenic for humans are included in 2 genera:
Flavivirus(yellow fever, tick-borne encephalitis virus, Omsk hemorrhagic fever virus, dengue fever virus, Japanese encephalitis virus, West Nile fever virus)
Hepacivirus(hepatitis C virus)
These are complex RNA genomic viruses of spherical shape, their diameter is 40-60 nm. The genome consists of a linear single-stranded plus-strand RNA surrounded by a capsid with cubic symmetry. The nucleocapsid contains one protein – V2. The nucleocapsid is surrounded by a supercapsid, the surface of which contains the V3 glycoprotein. The structural protein V1 is located on the inner side of the supercapsid.
Family Orthomyxoviruses (Orthomyxoviridae) includes the genus:
Influenzavirus(influenza virus, which includes 3 serotypes: A, B, C)
The diameter of the viral particle is 80-120 nm. The virion has a spherical shape. In the center of the virion there is a nucleocapsid, which has a helical type of symmetry. The genome of influenza viruses is a helix of single-stranded segmented minus-strand RNA. The capsid consists mainly of a protein - nucleoprotein (NP), as well as proteins of the polymerase complex (P). The nucleocapsid is surrounded by a layer of matrix and membrane proteins (M), which are involved in the assembly of the viral particle. On top of these structures is a supercapsid - an outer lipoprotein shell, which bears spines on its surface. The spines are formed by two complex glycoprotein proteins: hemagglutinin (H) and neuraminidase (N).
Family Paramyxoviruses (Paramyxoviridae), which includes 2 subfamilies:
Subfamily Paramyxoviruses:
Morbillivirus(measles virus)
Respirovirus(parainfluenza virus)
Rubulavirus(mumps virus, parainfluenza)
Subfamily Pneumoviruses:
Pneumovirus(respiratory syncytial virus (RS))
Metapneumovirus(PC virus)
The paramyxovirus virion has a spherical shape, a diameter of 150-300 nm, surrounded by an envelope with glycoprotein spikes. Under the shell is a helical nucleocapsid consisting of unfragmented linear single-stranded minus RNA bound by proteins: nucleoprotein (NP), polymerase-phosphoprotein (P) and large protein (L). The nucleocapsid is associated with matrix (M) protein located under the virion envelope. The virion envelope contains spikes - two glycoproteins: fusion protein (F), hemagglutinin-neuraminidase (HN) attachment protein, hemagglutinin (H) or (G) protein.
Family Rhabdoviruses (Rhabdoviridae) includes about 80 genera and causes diseases of animals and plants.
Lassavirus(rabies virus)
Vesiculovirus(vesicular stomatitis virus)
Virions have the shape of a cylinder with semicircular and flat ends (bullet shape), the size of virions is 130x300x60x80. They consist of a two-layer lipoprotein shell and a nucleocapsid of helical symmetry. The shell is lined with M-protein from the inside, and the spikes of glycoprotein G extend from it on the outside. The RNP of the nucleocapsid consists of genomic RNA and proteins: N - protein, which covers the RNA as a cover, L - protein and NS - protein, which are the transcriptase of the virus. The genome of rhabdoviruses is represented by single-stranded non-fragmented linear minus RNA.
Family Filoviruses (Filoviridae) contains two genera:
Genus of Marburg-like viruses(African hemorrhagic fever Marburg)
Genus of Ebola-like viruses(African hemorrhagic fever Ebola)
Viruses have the form of long filaments (80-1000 nm) with an envelope and single-stranded minus RNA enclosed in a capsid. Contains polymerase. The symmetry of the capsid is helical. The shell has spines (spicules).
Family Coronaviruses (Coronaviridae), includes 1 genus, uniting more than 10 species that cause diseases in humans and animals.
Coronavirus(causes damage to the respiratory organs, including SARS, gastrointestinal tract, nervous system)
Virions are round in size, 80-220 nm in size. The core of the virion is represented by a helical nucleocapsid containing single-stranded plus RNA. The nucleocapsid is surrounded by a lipid shell, covered on the outside with club-shaped projections - peplomeres. Ash meters give the viral particle the appearance of a solar corona. The virion shell contains glycoproteins E1 and E2, which are responsible for the adsorption of the virus on the cell and penetration into the host cell.
Family Retroviruses (Retroviridae), which includes 7 genera:
Alpharetrovirus(leukemia viruses, avian sarcoma, chicken Rous sarcoma)
Betaretrovirus(mouse mammary cancer virus, human endogenous retrovirus, simian virus)
Gammaretrovirus(sarcoma and leukemia viruses of mice, cats, primates)
Deltaretrovirus(bovine leukemia virus, human T-cell lymphotropic viruses)
Epsiloretrovirus(skin sarcoma virus)
Lentivirus(human immunodeficiency virus)
Spumavirus(foaming viruses of humans, monkeys, bovine syncytial virus)
Retroviruses have a spherical shape, size 80-130 nm. The virion has an envelope and a nucleocapsid core. The capsid is icosahedral. Reverse transcriptase is associated with the genome of single-stranded plus RNA. Viruses contain proteins: group antigen (gag), polymerase protein (pol) and envelope proteins (env). About 30 oncoantigens are known.
Family Arenaviruses (Arenaviridae) includes the genus:
Arenavirus(lymphocytic choriomeningitis viruses, Lasa, Junin, Machupo, Guanarito, causing severe hemorrhagic fevers)
The virion has a spherical or oval shape, with a diameter of about 120 nm. Outside, it is surrounded by a shell with club-shaped glycoprotein spikes GP1, GP2. Under the shell there are 12-15 cellular ribosomes, the capsid is spiral. The genome is represented by two segments (L, S) of single-stranded minus RNA, encoded by 5 proteins: L, Z, N, G.
Family Caliciviruses (Caliciviridae) contains Norwalk group gastroenteritis viruses and porcine vesicular exanthema virus.
The virion is non-enveloped, has an icosahedral capsid with 32 cup-shaped depressions (pits). The shape is spherical, diameter 27-38 nm. On the surface of the virion there are 10 protrusions formed by the edges of cup-shaped depressions. The genome is linear, single-stranded plus RNA.
Systematics and nomenclature of viruses. Principles of classification and taxonomy of viruses. Viroids, prions.
Virus classification principles:
Viruses make up the kingdom Vira, which is divided according to the type of nucleic acid into two subkingdoms - riboviruses and deoxyriboviruses. Subkingdoms are divided into families, which in turn are divided into genera. The concept of the type of viruses has not yet been clearly formulated, as well as the designation of different types.
As taxonomic characteristics, paramount importance is attached to the type of nucleic acid and its molecular biological characteristics: double-stranded, single-stranded, segmented, non-segmented, with repeating and inverted sequences, etc. However, in practical work, the characteristics of viruses obtained as a result of electron microscopic and immunological studies: morphology, structure and size of the virion, the presence or absence of an outer shell (supercapsid), antigens, resistance to high temperature, pH, detergents, etc.
Currently, human and animal viruses are included in 18 families. The belonging of viruses to certain families is determined by the type of nucleic acid, structure, integrity or fragmentation of the genome, as well as the presence or absence of an outer envelope. When determining membership in the retrovirus family, the presence of reverse transcriptase must be taken into account.
Viroids and prions
In addition to viruses, other very small mysterious infectious agents with unusual properties have been discovered in nature. These include viroids and prions.
Viroids. The name "viroid" was proposed in 1971 by T. Diener. It indicates that the symptoms of diseases caused by these agents in various plants are similar to the symptoms of diseases caused by viruses. However, viroids differ from viruses in at least the following four ways.
1. Viroids, unlike viruses, do not have a protein shell and consist only of an infectious RNA molecule. They do not have antigenic properties and therefore cannot be detected by serological methods.
2. Viroids are very small: the length of the viroid RNA molecule is 1 10"6 mm, it consists of 300-400 nucleotides. Viroids are the smallest reproductive units known in nature.
3. Viroid molecules are single-stranded circular RNAs. Only one other virus has such a ring structure - the delta hepatitis virus.
4. Viroid RNA molecules do not encode their own proteins, so their reproduction can occur either autocatalytically or with the participation of the host cell.
Since 1971, more than 10 different viroids have been discovered, differing in their primary structure, the range of hosts they affect, and the symptoms of the diseases they cause. All known viroids are built according to the same plan: 300-400 nucleotides form a ring, which is held in pairs of bases and forms a double-stranded rod-shaped structure with alternating short single- and double-stranded sections.
The question of the nature, origin of viroids and how they spread remains open. There is an assumption that viroids are formed from normal cellular RNAs, but no convincing evidence has been provided for this.
Prions. The name “prions” was proposed by S. Prusiner, who discovered them in 1982. Prions are low molecular weight proteins that do not contain nucleic acids that cause so-called transmissible spongiform encephalopathies. The latter are classified as a special group of slow lethal prion infections, which are characterized by a very long incubation period, a slowly progressive course, degenerative changes in the central nervous system, absence of signs of inflammation and a pronounced immune response, and death.
The synthesis of prions is controlled by the prgP gene, which is carried on the 20th chromosome in humans. Eighteen different mutations of this gene have been identified that are associated with various prion diseases.
Prions consist of a special protein that exists in the form of two isomers. One of them is the normal cellular prion protein - the PgPc isoform. It consists of 254 amino acid residues and has a molecular weight of 33-35 kDa. PrPtf is detergent soluble and sensitive to protein kinase K. It is believed to be involved in the regulation of the circadian cycle of many hormones. In healthy animals, its content is 1 μg/g of brain tissue (most of it is in neurons).
Another isomer of the prion protein PrPSc is anomalous, has the same molecular mass. It differs from PrPc in its secondary structure, is resistant to proteolysis, is insoluble in detergents, and is capable of self-aggregation and oligomerization. The conversion of prgPc to PrPSc occurs very slowly, but is accelerated in the presence of exogenous Orion. PrPSc prions are causative agents of slow prion infections.
The content of PrPbl in the brain tissue of sick animals is 10 times higher than in healthy animals.
There are 12 known nosological units of prion diseases, 6 of which are observed in animals (scrapie in sheep, spongiform encephalopathy in cattle, exotic ungulates and felines, chronic wasting disease in moose and transmissible encephalopathy in minks). Six diseases of prion etiology have been described in humans.
Kuru (Papuan curu - tremble, shake) was first described in 1957 by K. Gai-dushek among the cannibal Papuans in New Guinea. It is characterized by progressive cerebellar ataxia, general tremors, adynamia, as well as mental changes (euphoria, causeless laughter, etc.).
Creutzfeldt-Jakob disease (CJD - corticostriospinal degeneration) is found everywhere. Characterized by progressive dementia with symptoms of damage to the pyramidal and
extrapyramidal nerve tracts. In 1996, an epizootic of bovine spongiform encephalopathy (“rabies” of cows) began in England, and then in a number of other countries in Western Europe. It is associated with a violation of the natural nutritional patterns of animals: they began to receive substances obtained from the bones and meat waste of sheep and cows in the form of food additives. Contamination of the meat of such animals has caused CJD in humans. A new form of CJD has been described in England (designated VCJD). It differs from CJD in that it affects people under 40 years of age, as well as in its longer course and development of neuropathological changes not observed in the classical course of the disease.
Lethal familial insomnia - loss of sleep, hyperreactivity of the sympathetic system, progressive weakening of autonomic and endocrine cyclic time rhythms; observed in middle-aged people (about 45 years).
Gerstmann-Streisler syndrome (GSS) is a slow infection. Registered in the UK, USA, Japan and other countries of the world. It is characterized by degenerative lesions of the central nervous system, which manifest themselves in the formation of a sponge-like state, the formation of amyloid plaques throughout the brain. The disease is expressed in the development of slowly progressive ataxia and dementia. The pathogenesis has not been studied. The disease lasts a long time and ends in death.
Amyotrophic leukospongiosis is a slow human infection characterized by the progressive development of atrophic paresis of the muscles of the limbs and trunk, respiratory failure and ends in death.
Alpers syndrome is a slow prion infection. Observed mainly in childhood, characterized by symptoms indicating damage to the central nervous system.
Human prion diseases are characterized by 4 classic neuropathological signs: spongy changes (many oval vacuoles with a diameter of 1-50 microns in the gray matter of the brain), loss of neurons, astrocytosis and the formation of amyloid plaques.
It is assumed that prions play a role in the etiology of schizophrenia, myopathy and other human diseases. The nature of prions remains unclear. What they have in common with vises is their small size (they are able to pass through bacterial filters) and the inability to reproduce on artificial nutrient media; specific range of affected hosts; long-term persistence in cell culture obtained from the tissues of an infected host, as well as in the body of a sick person and animal. At the same time, they differ significantly from viruses: firstly, they do not have their own genome, therefore, they cannot be considered, unlike viruses, as living beings; secondly, they do not induce any immune response. Thirdly, prions have a significantly higher resistance than ordinary viruses to high temperatures (withstand boiling for 1 hour), UV radiation, ionizing radiation and various disinfectants; are insensitive to interferons and do not induce their synthesis.
According to S. Prusiner, there are two ways of transmission of the abnormal PrPSc prion: hereditary (mutations in the PrPSc gene) and transmissible, or infectious (dietary and nosocomial). In both cases, prion diseases are observed in the form of sporadic or group diseases.
K. Gaidushek in 1976 for the discovery of the infectious nature of prion diseases and S. B. Prusiner in 1997 for the discovery of prions and the development of prion theory were awarded Nobel Prizes.
Reproduction of viruses.
Reproduction of the virus in a cell occurs in several phases:
1) the first phase is the adsorption of the virus on the surface of a cell sensitive to the virus.
2) the second phase is the penetration of the virus into the host cell through viropexis.
3) the third phase is the “undressing” of virions, the release of the virus nucleic acid from the supercapsid and capsid. In a number of viruses, the penetration of nucleic acid into the cell occurs through the fusion of the virion envelope and the host cell. In this case, the second and third phases are combined into one.
4) the fourth phase is the synthesis of virion components. Virus nucleic acid is produced by replication. The viral mRNA information is translated to the cell's ribosomes, and a virus-specific protein is synthesized in them.
5) the fifth phase is virion assembly. Nucleocapsids are formed through self-assembly.
6) the sixth phase is the release of virions from the cell. Simple viruses, such as the polio virus, destroy the cell when they leave the cell. Complex viruses, such as the influenza virus, leave the cell by budding. The outer shell of the virus (supercapsid) is formed as the virus exits the cell. During this process, the cell remains alive for some time.
The described types of interaction between the virus and the cell are called productive, as they lead to the production of mature virions.
Another way - integrative - is that after the virus penetrates the cell and “undresses”, the viral nucleic acid integrates into the cellular genome, that is, it is integrated at a certain place into the cell chromosome and then replicates along with it in the form of a so-called provirus. For DNA and RNA viruses, this process occurs differently. In the first case, the viral DNA integrates into the cellular genome. In the case of RNA-containing viruses, reverse transcription occurs first: DNA is formed on the viral RNA matrix with the participation of the “reverse transcriptase” enzyme, which is integrated into the cellular genome. The provirus carries additional genetic information, so the cell acquires new properties. Viruses capable of carrying out this type of interaction with a cell are called integrative. Integrative viruses include some oncogenic viruses, hepatitis B virus, herpes virus, human immunodeficiency virus, and temperate bacteriophages.
In addition to ordinary viruses, there are prions - protein infectious particles that do not contain nucleic acid. They have the form of fibrils up to 200 nm in size. They cause slow infections in humans and animals that damage the brain: Creutzfeldt-Jakob disease, kuru, scrapie and others.
4) Features of virus reproduction depending on the type of nucleic acid (+ and – RNA). Types of interaction between viruses and cells: productive, abortive, integrative.
Depending on the type of nucleic acid, this process occurs as follows.
1) reproduction occurs in the nucleus: adenoviruses, herpes, papovaviruses. The cell's DNA-dependent RNA polymerase is used.
2) reproduction occurs in the cytoplasm: viruses have their own DNA-dependent RNA polymerase.
1) riboviruses with a positive genome (plus-strand): picorna-, toga-, coronaviruses. There is no transcription.
2) riboviruses with a negative genome (minus-strand): influenza, measles, mumps, ortho-, paramyxoviruses.
(-)RNA, mRNA-protein (mRNA-complementary (-)RNA). This process occurs with the participation of a special viral enzyme - virion RNA-dependent RNA polymerase (such an enzyme cannot exist in a cell).
3) retroviruses (-)RNA, DNA, mRNA-protein (mRNA is homologous to RNA). In this case, the process of DNA formation on the basis of (-)RNA is possible with the participation of an enzyme - RNA-dependent DNA polymerase (reverse transcriptase or reversetase).
Detection of viral Ags
ELISA. Currently, commercial kits have already appeared for identifying Ag from some pathogens, allowing them to be identified within 5-10 minutes. To detect Ag, known ATs are sorbed on the solid phase and serum containing Ag is added; After incubation, unbound Ag is decanted, the system is washed and labeled AT, specific to sorbed AT, is added. The incubation and washing procedure is repeated, a chromogenic substrate is added, a positive result is recorded when the color of the system changes.
DNA hybridization- a highly specific method that allows you to identify the genome of the virus after its hybridization with complementary DNA molecules. Enzymes and isotopes are used as markers. The method determines the ability of viral DNA to hybridize with labeled complementary DNA; the specificity of the method is directly proportional to the length of the I complementary chain. The method of in situ hybridization of nucleic acids is promising. To set up the reaction, labeled DNA is applied to tissue biopsies (including those fixed in formalin or embedded in paraffin blocks) and the interaction with complementary DNA is recorded. The method is used to detect herpes simplex viruses, human papilloma, Epstein-Barr, etc.
PCR. The method significantly increases the sensitivity of the hybridization method, increasing the content of viral DNA in the material obtained from the patient, and also speeds up the time to obtain results.
Lesson No. 7. General characteristics of viruses and features of their reproduction. DNA and RNA viruses.
1) Structure (structure, chemical composition) of viruses. Types of nucleocapsid symmetry.
Morphology and structure Viruses are studied using an electron microscope, since their sizes are small and comparable to the thickness of the bacterial shell.
Form virions can be different: rod-shaped (tobacco mosaic virus), bullet-shaped (rabies virus), spherical (poliomyelitis viruses, HIV), in the form of a sperm (many bacteriophages). There are simple and complex viruses.
Simple, or non-enveloped, viruses consist of a nucleic acid and a protein shell called a capsid. The capsid consists of repeating morphological subunits - capsomeres. The nucleic acid and capsid interact with each other to form the nucleocapsid.
Complex, or enveloped, viruses are surrounded on the outside of the capsid by a lipoprotein shell (supercapsid, or peplos). This shell is a derived structure from the membranes of a virus-infected cell. The virus shell contains glycoprotein spikes, or spines (peplomeres). Under the shell of some viruses there is a matrix M protein.
Phenotypic mixing is quite widespread among closely related non-enveloped viruses, such as polio viruses types 1 and 2, ECHO and Coxsackie viruses, and other picornaviruses. Thus, non-mutation hybrid viruses are full-fledged virions. Like mutant viruses, they arise through complementation, and not as a result of crossing genomes, like recombinants. The states of heterozygosity and transcapsidization of viruses are unstable and quickly disappear during passages. The biological significance of heterozygotes is not clear. Transcapsidization can provide hybrid viruses with a wide range of hosts and overcome interspecies barriers.
Capsid and supercapsid protect virions from environmental influences, determine selective interaction (adsorption) with cells, determine the antigenic and immunogenic properties of virions. The internal structures of viruses are called the core.
Symmetry type. The capsid or nucleocapsid may have a helical, icosahedral (cubic) or complex type of symmetry. Icosahedral the type of symmetry is due to the formation of an isometrically hollow body from a capsid containing viral nucleic acid (for example, in hepatitis A, herpes, polio viruses). Spiral the type of symmetry is due to the helical structure of the nucleocapsid (for example, in the influenza virus).
Inclusions- accumulation of virions or their individual components in the cytoplasm or nucleus of cells, detected under a microscope with special staining. Variola virus forms cytoplasmic inclusions - Guarnieri bodies; herpes viruses and adenoviruses are intranuclear inclusions.
Dimensions viruses are determined using electron microscopy, ultrafiltration through filters with a known pore diameter, and ultracentrifugation. One of the smallest viruses is the polio virus (about 20 nm), the largest is smallpox (about 350 nm).
Viruses have a unique genome, since they contain either DNA or RNA. Therefore, a distinction is made between DNA-containing and RNA-containing viruses. They are usually haploid, i.e. have one set of genes. The genome of viruses is represented by various types of nucleic acids: double-stranded, single-stranded, linear, circular, fragmented. Among RNA-containing viruses, viruses with a positive (plus-strand RNA) genome are distinguished. The plus-strand RNA of these viruses performs hereditary and messenger RNA (mRNA) functions. There are also RNA viruses with a negative (minus-strand RNA) genome. The minus strand RNA of these viruses performs only a hereditary function.
Intramolecular recombinations in viruses, like other microorganisms, are realized by the break-reunion mechanism, and in RNA viruses with a segmented genome - by gene mixing. In general, there are two groups of recombinations in viruses: recombination in DNA viruses and recombination-reassortment in RNA viruses with a segmented genome.
Among the genetic recombinations of DNA viruses, recombinations are distinguished:
1) between two wild types of viruses with intact (Latin intactus - untouched), i.e. complete, genomes;
2) between the wild type and its mutant variant;
3) between variants of wild-type virus mutants.
From lat. "virus" - poison
Viruses are an extracellular form of life that has its own genome and is capable of reproducing only in the cells of living organisms.
A virion (or viral particle) consists of one or more DNA or RNA molecules enclosed in a protein shell (capsid), sometimes also containing lipid and carbohydrate components
The diameter of viral particles (also called virions) is 20-300 nm. Those. they are much smaller than the smallest of prokaryotic cells. Since the sizes of proteins and some amino acids. are in the range of 2-50 nm, then the viral particle could be considered simply a complex of macromolecules. Due to their small size and inability to reproduce themselves, viruses are often classified as “non-living”.
They say “A virus is an intermediate form of life, or non-life,” because. outside the host cell it turns into a crystal.
They say: c. this is a transition from chemistry to life
Life cycle the virus begins
1. from penetration into the cell.
2. To do this, it binds to specific receptors on its surface and
a) either introduces its nucleic acid into the cell, leaving the virion proteins on its surface,
b) or penetrates entirely as a result of endocytosis. In the latter case, after the virus penetrates into the cell, it is “undressed” - the release of genomic nucleic acids from the envelope proteins.
3. As a result of this procedure, the viral genome becomes accessible to cell enzyme systems that ensure the expression of viral genes.
4. It is after the penetration of the viral genomic nucleic acid into the cell that the genetic information contained in it is deciphered by the host’s genetic systems and is used to synthesize the components of viral particles.
Compared to the genomes of other organisms, the viral genome is relatively small and encodes only a limited number of proteins, mainly capsid proteins and one or more proteins involved in viral genome replication and expression. Necessary metabolites and energy are supplied by the host cell.
DNA viruses carry either single- or double-stranded DNA as genetic material, which can be either linear or circular. DNA encodes information about all the proteins of the virus. Viruses are classified depending on whether their DNA is single or double stranded and whether the host cell is pro- or eukaryotic. Viruses that infect bacteria are called bacteriophages.
1 - smallpox viruses; 2 - herpes viruses; 3 – adenoviruses; 4 - papovaviruses; 5 - hepadnaviruses; 6 - parvoviruses;
First group - double-stranded DNA viruses
- replication is carried out according to the scheme: DNA -»RNA -> DNA.
- they got the name retroid viruses.
- p Representatives of this group of viruses are hepatitis B virus and cauliflower mosaic virus.
1. Replication of the DNA genome of these viruses is carried out through intermediate RNA molecules:
2. RNA molecules are formed as a result of transcription of viral DNA in the cell nucleus by the host enzyme DNA-dependent RNA polymerase.
3. Only one of the viral DNA strands is transcribed.
4. DNA synthesis on an RNA template occurs as a result of a reaction catalyzed by reverse transcriptase; first the (-) strand of DNA is synthesized,
5. and then on the newly synthesized (-) DNA strand, the same enzyme builds a (+) strand.
Overall, the general pattern of genome replication of retroid viruses is strikingly similar to that of retroviruses. Apparently, this similarity also has an evolutionary basis, since the primary structure of the reverse transcriptases of these viruses reveals a certain similarity to each other.
Second group - double-stranded DNA viruses
- Replication is carried out according to the DNA -> DNA scheme.
- from the genome of these viruses in the infected cell, DNA-dependent RNA polymerase transcribes mRNA molecules (i.e. (+) RNA),
mRNA (i.e. (+) RNA) takes part in the synthesis of viral proteins,
Reproduction of the viral genome is carried out by the enzyme DNA-dependent DNA polymerase: (±) dna → (+) RNA
In some cases, cellular enzymes produce both mRNA and DNA; in other cases, viruses use their own enzymes. It happens that both enzymes serve the process of replication and transcription. This group includes herpes viruses, smallpox, etc.
Herpes virus
Smallpox is the natural enemy of AIDS (there is no smallpox - there is AIDS). There is information about AIDS in the Old Testament. Our genome contains genetic marks from previous AIDS pandemics
Viral diseases are periodic: smallpox → LEPROSE → PLAGUE → †
Third group - viruses with single-stranded DNA, either negative or positive polarity.
- Once inside the cell, the viral genome first turns into a double-stranded form,
This conversion is ensured by cellular DNA-dependent DNA polymerase:
or (±) DNA → (+) RNA
Transcription and replication at subsequent stages occurs in the same way as for viruses, with a (±) DNA genome.
Structure of the virus: it is a DNA molecule in a protein shell called a capsid. However there are many different options the structure of viruses: from simply protein-coated DNA (for example, bacteriophage Pf1) to complex macromolecular complexes surrounded by membrane structures, for example, smallpox virus. If a virus has a membrane, it is said to be enveloped, and if there is no membrane, then the virus is called “undressed.” There are four main types of capsids: helical, icosahedral, complex without a shell, complex with a shell. (see presentation)
Helical capsids
- usually found in filamentous viruses.
They are formed by self-assembly of asymmetric protein subunits (capsomeres), uniting into a tubular structure with helical symmetry (for example, Pf1).
The subunits are in most cases homogeneous, so that the surface of the virion consists of many copies of the same protein, although other proteins may be located under the outer capsid.
The DNA in such viruses is either stretched out or can be tightly coiled in complex with special binding proteins.
Icosahedral capsids
Characteristic of most spherical DNA viruses
An icosahedron is a polyhedron with twenty triangular faces, having cubic symmetry and approximately spherical shape.
The vertices of the triangles join to form the twelve vertices of the icosahedron;
At the junctions there are usually pentameric protein structures - pentons; There may also be areas where protein threads are formed, often associated with vertices (for example, in f X174 transparent 1).
The faces of the icosahedron are filled with other protein subunits, usually grouped into hexameric structures - hexons (for example, in adenovirus transparent 1).
The number of subunits required to fill the faces is determined by the size of the virion as a whole, and different icosahedral viruses therefore contain different numbers of hexons - usually with a constant number of pentons.
The DNA is usually tightly coiled within the capsid;
Sometimes it is associated with proteins or polypeptides that can stabilize its structure.
Complex capsids without shell
Typical for bacteriophages:
They consist of parts with different types symmetry.
In bacteriophage T2, for example, DNA is located in the icosahedral head, and tubular and fibrillar structures are used to “recognize” the bacterium and introduce DNA into it (lysozyme, located at the distal end of the tail process, also participates in recognition).
Complex enveloped capsids
Only viruses of eukaryotic cells have it.
In them, DNA-protein complexes are surrounded by one or more protein layers and an outer membrane, almost all of the protein components of which are viral in origin, and the lipid structures are cellular.
Infection is the process by which a virus invades a host cell and “tunes” its metabolic apparatus to reproduce virions.
Cells infected with a virus either remain alive (then the virus is said to be non-virulent),
Or they undergo lysis, leading to the release of viral particles.
The constant result of cell infection DNA-containing bacteriophages is lysis.
- DNA-containing animal viruses rarely cause lysis; however, cells can die due to chromosomal damage caused by infection, as a result of the body's immunological reaction, or simply as a result of the virus disrupting normal cellular functions.
Virus replication is a clearly defined cycle that ultimately leads, after the synthesis of new viral protein molecules and a large number of copies of viral DNA, to the formation of mature viral particles. For bacterial viruses, the entire cycle can be completed in less than an hour, while for many animal viruses it takes more than one day.
Virus adsorption on the host cell – the first stage of infection. It occurs at specific receptor sites (protein or lipid) on the cell surface, which are recognized by special protruding parts of the virion and to which it is firmly attached. In viruses without an envelope, such parts can be protein appendages (for example, in adenovirus and bacteriophage T2), and in viruses with an envelope, these are usually proteins immersed in the viral membrane. During the adsorption process, in particular, such protein-protein interactions take place, the result of which is the initiation of the stage of DNA penetration into the cell.
Penetration The transfer of viral DNA into the host cell occurs differently for different viruses. The DNA of many bacteriophages, for example, bacteriophage T2: the protein rod is flattened, like a telescopic structure, and the DNA is “injected” into the bacterium. From animal viruses, DNA usually passes into the cell as a result of the fusion of the outer layer of the virion with the cell membrane. Unlike the DNA of most bacteriophages, the DNA of animal viruses always enters the cell along with the proteins immediately adjacent to it; the subsequent release of DNA from these proteins is carried out with the help of enzymes.
Transcription and replication The genetic material of the virus is usually carried out with the participation of host cell enzymes. Viral DNA is first copied by host cell RNA polymerases, resulting in mRNA, which is then translated. On some viral DNA molecules, DNA copies are also synthesized, using either cellular or virus-encoded DNA polymerase. These DNA copies are subsequently used in the assembly of viral particles. In some cases, for example, in the T4 bacteriophage, the very first newly synthesized viral mRNA molecules are translated with the formation of special proteins that modify the host cell polymerases in such a way that they stop the transcription of cellular genes without losing the ability to transcribe viral ones. In what part of the cell do the processes of transcription and replication of viral DNA of eukaryotic viruses take place: in the nucleus or cytoplasm? In some, transcription and replication occurs in the nucleus of the host cell (for example, in the herpes virus), while in others - in the cytoplasm, for example, in poxyviruses.
Broadcast viral mRNA on host cell ribosomes leads to the formation of viral proteins. Some of these proteins are subsequently used to build capsids, others bind to viral DNA, stabilizing it (in many animal viruses), while others, although they will never be part of mature virions, participate in the process of their assembly as enzymes (for example, in the bacteriophage T2)
Assembly The synthesis of a virus from its components in the host cell can occur spontaneously (self-assembly), but may also depend on the participation of auxiliary proteins. The viral DNA is usually covered by a layer of protein called the capsid. The capsid, in turn, can be enclosed in a membrane structure, usually received by the virion from the host cell: leaving the cell by budding from it, the viral particle finds itself surrounded by a plasma membrane.
1. Polyomaviruses - simian virus SV40, mouse polyoma virus and human viruses BK and JC.
2. Papillomaviruses - 16 human papillomaviruses and many animal papillomaviruses.
3. Adenoviruses - 37 human viruses, many animal adenoviruses (for example, 24 monkey viruses and 9 cattle viruses).
4. Herpoviruses – human herpes simplex viruses, human cytomegalovirus, Epstein-Barr virus and oncogenic viruses of primates, horses, chickens, rabbits, frogs.
5. Viruses similar to hepatitis B virus are human hepatitis B virus, North American woodchuck hepatitis, ground squirrel hepatitis and duck hepatitis.
1 - paramyxoviruses; 2 - influenza viruses; 3 - coronaviruses; 4 - arenaviruses; 5 - retroviruses; 6 - reoviruses; 7 - picornaviruses; 8 - capiciviruses; 9 - rhabdoviruses; 10 - togaviruses, flaviviruses; 11 - bunyaviruses
The genomes of almost all known RNA-containing viruses are linear molecules; they can be conveniently divided into 3 groups.
First group- these are single-stranded genomes of positive polarity, i.e. with a nucleotide sequence corresponding to that of mRNA.
Such genomes are referred to as (+) RNA.
Viral (+) RNA genomes encode several proteins, including RNA-dependent RNA polymerase (replicase), which is capable of synthesizing RNA molecules without the participation of DNA.
With the help of this enzyme, the (-) RNA strands of the phage are first synthesized,
Then, in the presence of a special protein called a “host factor,” the replicase synthesizes the (+) strand of RNA.
At the final stage, virions are formed from accumulated viral proteins and (+) RNA.
A simplified diagram of this process is as follows:
(+) RNA (-) RNA
Single-stranded (+) RNA genome is characteristic of
a) phage Qβ,
b) tobacco mosaic viruses,
Tobacco mosaic virus is an example of a + single-stranded plant virus; the virus does not have an envelope, is helical, contains 2130 identical capsid protein molecules and one strand of RNA. RNA is located in a helical groove surrounded by protein subunits and is held in place by numerous weak bonds.
Infectious process proceeding according to the diagram (transparent 2 below), consists in the penetration of the virus into the plant cell with the subsequent rapid loss of its capsid. Then, as a result of direct translation of +single-stranded viral RNA by the ribosomes of the host cell, several proteins are formed, some of which are necessary for the replication of the viral genome.
Replication carried out by RNA replicase, which produces copies of RNA for new virions. Synthesis of the capsid protein occurs only after the RNA that has infected the cell has undergone some modification, making it possible for the cell's ribosomes to attach to the portion of the RNA that encodes this protein. Virion assembly begins with the formation of discs from the capsid protein. Two such protein disks, arranged concentrically, form a biscuit-like structure, which, when RNA binds to it, takes on the shape of a helix. Subsequent attachment of protein molecules continues until the RNA is completely covered. In its final form, the virion is a cylinder 300 nm long.
3) polio,
4) tick-borne encephalitis.
Second group- these are single-stranded genomes with negative polarity, i.e. (-) RNA genomes.
Since (-) RNA cannot perform the functions of mRNA, to form “its” mRNA, the virus introduces into the cell not only the genome, but also an enzyme that can remove complementary copies from this genome according to the following scheme:
(-) RNA (+) RNA
This viral enzyme (RNA-dependent RNA polymerase synthesized in the previous reproduction cycle) is packaged in the virion in a form convenient for delivery into the cell.
The infectious process begins with the viral enzyme copying the viral genome, forming (+) RNA, which acts as a template for the synthesis of viral proteins, including RNA-dependent RNA polymerase, which is part of the resulting virions
Viruses with a negative RNA genome include
a) influenza viruses,
c) rabies
d) yellow dwarfism of potatoes, etc.
Influenza virus diagram
Influenza virus is an example of a “-”-single-stranded RNA virus. It has a shell and a spiral core. The core consists of eight “-” RNA segments, which, in combination with proteins, form helical structures. Each segment encodes one of the viral proteins. The virus contains the largest amount of matrix protein, which is located on the inner side of the shell and gives it stability. All envelope proteins are encoded by viral RNA, whereas lipids are cellular in origin (see DNA viruses, assembly). The main shell proteins are hemagglutinin and neuraminidase.
Infectious process proceeds according to the scheme (transparent 2 below) begins with the attachment of the virus to the surface of the host cell through hemagglutinin. Then, the envelope fuses with the cell membrane, the nucleoprotein core (nucleocapsid) enters the cell, and the virus-encoded RNA-dependent RNA polymerase synthesizes + strands of mRNA on the viral “-” strands, after which viral proteins are produced on the ribosomes of the host cell. Some of these proteins play an important role in viral genome replication.
Replication occurs in the nucleus, where, with the help of the same, but probably modified RNA polymerase, “-” RNA chains are formed. After nucleocapsid proteins enter the nucleus, nucleocapsid assembly occurs. The nucleocapsid then passes through the cytoplasm, attaching envelope proteins along the way, and leaves the cell, budding from its plasma membrane. It is believed that neuraminidase is involved in the budding process.
Third group constitute double-stranded genomes, (±) RNA genomes.
Known double-stranded genomes are always segmented (i.e., composed of several different molecules).
This includes reoviruses. Their reproduction proceeds according to a variant close to the previous one. Along with the viral RNA, the viral RNA-dependent RNA polymerase enters the cell, which ensures the synthesis of (+) RNA molecules. In turn, (+) RNA ensures the production of viral proteins on the ribosomes of the host cell and serves as a template for the synthesis of new (-) RNA chains by the viral RNA polymerase
Chains (+) and (-) RNA, complexing with each other, form a double-stranded (±) An RNA genome that is packaged into a protein shell.
- Reoviruses birds (from the English respiratory respiratory, enteric intestinal, orphan orphan) are icosahedral viruses without an envelope, the protein capsid of which consists of two layers - outer and inner. Inside the capsid are 10 or 11 segments of double-stranded RNA.
Reoviruses infect the respiratory and intestinal tracts of warm-blooded animals (humans, monkeys, cattle, small ruminants, bats,
Infectious process begins with the penetration of RNA into the cell and then proceeds in accordance with the diagram (transparent 2 - below). After partial destruction of the outer capsid by lysosome enzymes, the RNA in the thus formed subviral particle is transcribed, its copies leave the particle and combine with ribosomes. The host cell then produces proteins necessary for the formation of new viral cysts.
Replication RNA viruses occur by a conserved mechanism. One of the strands of each RNA segment serves as a template for the synthesis of a large number of new + strands. On these + chains, – chains are then formed as on a matrix; the + and – chains do not diverge, but remain together in the form of double-chain molecules. the assembly of new viral particles from newly formed + and – segments and capsid proteins is somehow connected with the miotic spindle of the host cell.
This includes viruses in which the genome replication cycle can be divided into two main reactions: RNA synthesis on a DNA template and DNA synthesis on an RNA template.
In this case, the composition of the viral particle as a genome can include either RNA (retroviruses ( Retroviridae– from REversed TRanscription)), or DNA (retroid viruses).
The viral particle contains two molecules of genomic single-stranded (+) RNA.
The viral genome encodes an unusual enzyme (reverse transcriptase, or revertase), which has the properties of both RNA-dependent and DNA-dependent DNA polymerases.
Only in 1970 did the American scientists G. Temin and Mitsutani and, independently of them, D. Baltimore solve this riddle. They proved the possibility of transferring genetic information from RNA to DNA. This discovery overturned the central dogma of molecular biology that genetic information can only be transferred in the DNA-RNA-protein direction. It took G. Temin five years to discover the enzyme that transfers information from RNA to DNA - RNA-dependent DNA polymerase. This enzyme was named reverse transcriptase. G. Temin managed not only to obtain DNA fragments complementary to a given RNA chain, but also to prove that DNA copies can be integrated into the DNA of cells and transmitted to offspring.
This enzyme enters the infected cell along with the viral RNA and ensures the synthesis of its DNA copy, first in single-stranded form [(-) DNA], and then in double-stranded form [(±) DNA]:
The viral genome in the form of a normal DNA duplex (the so-called proviral DNA) is integrated into the chromosome of the host cell.
As a result, the double-stranded DNA of the virus is essentially an additional set of genes in the cell that replicates along with the host DNA when it divides.
To form new retroviral particles, proviral genes (virus genes in the host chromosomes) are transcribed in the cell nucleus by the host transcription apparatus into (+) RNA transcripts.
Some of them become the genome of the new “offspring” of retroviruses, while others are processed into mRNA and used to translate proteins necessary for the assembly of viral particles
This group includes
a) human immunodeficiency virus (HIV)
Information about AIDS is in the Old Testament
Our ganome contains genetic marks from previous AIDS pandemics
