I. History of discovery and methods for studying viruses

I. History of discovery and methods for studying viruses

In this article we will talk about the history of the discovery of viruses. This is an interesting topic that does not receive much attention in the modern world, but in vain. First, we will understand what the virus itself is, and then we will talk about other aspects of this issue.

Virus

A virus is a noncellular infectious organism that can only reproduce inside living cells. By the way, from Latin this word is translated literally as “poison”. These formations can affect all types of living organisms, from plants to bacteria. There are also viruses that can only reproduce within their other counterparts.

Study

Research began in 1892. Then Dmitry Ivanovsky published his article in which he described a pathogen of tobacco plants. The virus was discovered by Martin Beijerinck in 1898. Since then, scientists have described about 6,000 different viruses, although they believe that there are more than 100 million of them. Note that these formations are the most numerous biological form that is present in any ecosystem on Earth. They are studied by virology, namely the branch of microbiology.

Short description

Note that while the virus is outside the cell or in the process of nucleation, it is an independent particle. Typically consists of three components. The first is genetic material, which is represented by DNA or RNA. Note that some viruses may have two types of molecules. The second component is the protein shell, which protects the virus itself and its lipid shell. By its presence, viruses are distinguished from similar infectious bacteria. Depending on the type of nucleic acid, which is essentially genetic material, viruses are divided into DNA-containing and RNA-containing viruses. Previously, prions were classified as viruses, but then it turned out that this was an erroneous opinion - these are ordinary pathogens that consist of infectious material and do not contain nucleic acids. The shape of the virus can be very diverse: from spiral to much more complex structures. The size of these formations is approximately one hundredth of a bacterium. However, most viruses are so small that they cannot be clearly seen even with a light microscope.

Life form

Appearance

The history of the discovery of the virus is silent about how they appeared on the evolutionary tree. This is indeed a very interesting question that has not yet been sufficiently studied. It is believed that some viruses could have been formed from small DNA molecules that could be transmitted between cells. There is another possibility that viruses originated from bacteria. At the same time, due to their evolution, they are an important element in horizontal gene transfer and provide genetic diversity. Some scientists consider such formations to be a distinctive form of life due to certain characteristics. First, there is the genetic material, the ability to reproduce and evolve naturally. But at the same time, viruses do not have very important characteristics of living organisms, for example, cellular structure, which is the main property of all living things. Due to the fact that viruses have only part of the characteristics of life, they are classified as forms that exist on the edge of life.

Spreading

Viruses can spread in different ways; there are many different ways. They can be transmitted from plant to plant by insects that feed on plant juices. An example is aphids. In animals, viruses can be spread by blood-sucking insects that carry bacteria. As we know, the influenza virus spreads in the air through sneezing and coughing. For example, rotavirus and norovirus can be transmitted through contact with contaminated food or liquid, that is, through the fecal-oral route. HIV is one of the few viruses that can be transmitted through blood transfusions and sexual contact.

Each new virus has certain specificity in relation to its hosts. In this case, the host range can be narrow or wide, depending on how many cells were affected. Animals respond to infection with an immune response that destroys pathogenic organisms. Viruses as a form of life are quite adaptable, so they are not so easy to destroy. In humans, the immune response can be a vaccine against specific infections. However, some organisms can bypass a person's internal security system and cause chronic disease. These are the human immunodeficiency virus and various hepatitis. As is known, antibiotics cannot affect such organisms, but despite this, scientists have developed effective antiviral drugs.

Term

But before we talk about the history of the discovery of viruses, let's talk about the term itself. As we know, the word is literally translated as “poison.” It was used in 1728 to identify an organism that is capable of causing an infectious disease. Before Dmitry Ivanovsky discovered viruses, he coined the term “filterable virus,” by which he meant a pathogenic agent of a non-bacterial nature that can pass through various filters in the human body. The well-known term “virion” was coined in 1959. It means a stable viral particle that has left the cell and can independently infect further.

History of research

Viruses became something new in microbiology, but data about them accumulated gradually. Advances in science have made it clear that not all viruses are caused by pathogens, microscopic fungi, or protists. Note that researcher Louis Pasteur was never able to find the agent that causes rabies. Because of this, he assumed that it was so small that it was impossible to examine it under a microscope. In 1884, Charles Chamberlant, a famous microbiologist from France, invented a filter whose pores were much smaller than bacteria. Using this tool, you can completely remove bacteria from a liquid. In 1892, Russian microbiologist Dmitry Ivanovsky used this apparatus to study a species that was later named tobacco mosaic virus. The scientist's experiments showed that even after filtration, infectious properties are retained. He suggested that the infection could be caused by a toxin released by bacteria. However, then the man did not develop this idea further. At that time, the ideas were popular that any pathogen could be identified using a filter and grown in a nutrient medium. Note that this is one of the postulates of the theory of disease at the microbial level.

"Ivanovsky Crystals"

Using an optical microscope, Ivanovsky observed infected plant cells. He discovered crystal-like bodies, which are now called virus clusters. However, then this phenomenon was called “Ivanovsky crystals.” A Dutch microbiologist in 1898, Martin Beijerinck, repeated Ivanovsky's experiments. He decided that the infectious material that passes through the filter was a new form of agent. At the same time, he confirmed that they can reproduce only in dividing cells, but experiments did not reveal that they were particles. Martin then called these particles "soluble living microbes," literally speaking, and again began to use the term "virus." The scientist argued that viruses are liquid in nature, but this conclusion was refuted by Wendell Stanley, who proved that viruses are essentially particles. At the same time, Paul Frosch and Friedrich Leffler discovered the first animal virus, namely the causative agents of foot-and-mouth disease. They passed it through a similar filter.

Virus life cycle and further research

At the beginning of the last century, English bacteriologist Frederick Twort discovered a group of viruses that could multiply in bacteria. Now such organisms are called bacteriophages. At the same time, Canadian microbiologist Felix Darelle described viruses that, when in contact with bacteria, can form a space around themselves with dead cells. He made suspensions, thanks to which he was able to determine the lowest concentration of the virus at which not all bacteria die. Having made the necessary calculations, he was able to determine the initial number of viral units in the suspension.

The life cycle of the virus was actively studied at the beginning of the last century. Then it became known that these particles could have infectious properties and pass through the filter. However, they need a living host to reproduce. The first microbiologists conducted research on viruses only on plants and animals. In 1906, Ross Granville Harrison invented a unique method of growing tissue in lymph.

Breakthrough

At the same time, new viruses were being discovered. Their origin still remained and remains a mystery today. Note that the discovery of the influenza virus belongs to the American researcher Ernest Goodpasture. In 1949, a new virus was discovered. Its origin was unknown, but the organism was grown on human embryonic cells. Thus, the first poliovirus grown on living human tissue was discovered. Thanks to this, the most important polio vaccine against polio was created.

The image of viruses in microbiology appeared thanks to the invention of the electron microscope by engineers Max Knoll and Ernst Ruska. In 1935, an American biochemist conducted a study that proved that the tobacco mosaic virus consists mainly of protein. A little later, this particle was divided into protein and RNA components. It was possible to crystallize the mosaic virus and study its structure in much more detail. The first X-ray image was obtained in the late 1930s thanks to the scientists Barnal and Fankuchen. The breakthrough of virology occurred in the second half of the last century. It was then that scientists discovered more than 2,000 different types of viruses. In 1963, the hepatitis B virus was discovered by Blumberg. In 1965, the first retrovirus was described.

To summarize, I would like to say that the history of the discovery of viruses is very interesting. It allows you to understand many processes and understand them in more detail. However, it is necessary to have at least a superficial understanding in order to keep up with the times, because progress is developing by leaps and bounds.


Hypotheses about the origin of viruses

Throughout the development of virus science, three main hypotheses have been put forward.

The possibility of degenerative evolution has been repeatedly established and proven, and perhaps the most striking example of it is the origin of some cellular organelles of eukaryotes from symbiotic bacteria. For example, it can be considered established that the chloroplasts of protozoa and plants come from the ancestors of today's blue-green bacteria, and mitochondria from the ancestors of purple bacteria. Therefore, such a possibility cannot be excluded for the origin of viruses, especially such large, complex and autonomous ones as the smallpox virus.

Yet the world of viruses is too diverse to recognize the possibility of such a deep degenerative evolution for most of its representatives, from smallpox viruses, herpes viruses to reoviruses, not to mention such autonomous genetic structures as plasmids.

Ring spot virus. Photo: hs_rattanpal

The diversity of genetic material in viruses is one of the arguments in favor of the origin of viruses from precellular forms. Indeed, the genetic material of viruses “exhausts” all its possible forms: single- and double-stranded RNA and DNA, their linear, circular and fragmentary types. And yet, the diversity of genetic material in viruses is more likely to indicate the polyphyletic origin of viruses than to the preservation of ancestral precellular forms, the genome of which evolved along an unlikely path from RNA to DNA, from single-stranded forms to double-stranded ones, etc.

The third hypothesis of 20-30 years seemed unlikely and even received the ironic name of the runaway genes hypothesis. However, it is precisely this theory that easily explains not only the quite obvious polyphyletic origin of viruses, but also the commonality of such diverse structures as full-fledged and defective viruses, satellites and plasmids. This concept also implies that the formation of viruses was not a one-time event, but occurred many times and continues to occur at the present time. In ancient times, along with the formation of cellular forms, the formation of non-cellular forms also occurred, represented by viruses - autonomous, but cell-dependent genetic structures. Currently existing viruses are products of evolution, both of their most ancient ancestors and of recently emerged autonomous genetic structures.

History of the discovery of viruses

In the 80s of the 19th century in the south of Russia, tobacco plantations were subjected to a formidable invasion. The tops of plants died off, light spots appeared on the leaves, the number of affected fields increased from year to year, and the cause of the diseases was unknown.

An expedition was sent to Bessarabia and Ukraine, which included D.I. Ivanovsky and V.V. Polovtsev.

In 1892, Ivanovsky discovered a new kingdom of living beings.

Ivanovsky spent several years searching for the causative agents of the disease. He collected facts, made observations, asked peasants about the symptoms of the disease, and experimented. Experiments have shown that the problem is not in the components of the plant - the root system, seeds, pollen or flowers: the pathogen affects the plants in a different way. Then the young scientist performs a simple experiment. He collects diseased leaves, crushes them and buries them in areas with healthy plants. After some time, the plants become sick. So, the path from a diseased plant to a healthy one has been found. The pathogen is transmitted by leaves that fall into the soil, overwinters and infects crops in the spring.

But he never learned anything about the pathogen itself. His experiments showed only one thing: there is something infectious in the juice. During these years, several more scientists in the world struggled to identify this “something.” A. Mayer in Holland proposed that the infectious source is bacteria. However, Ivanovsky proved that Mayer was mistaken in believing that bacteria were carriers of the disease. Having filtered the infectious juice through fine-pored porcelain filters, he deposited bacteria on them. Now the bacteria have been removed... but the juice remains infectious.

So, this incomprehensible agent that causes the disease does not reproduce in artificial media, penetrates through the finest pores, and dies when heated. Filterable poison. This was the scientist's conclusion. But poison is a substance, and the causative agent of tobacco disease was a creature. It reproduced well in plant leaves.

Thus, Ivanovsky discovered a new kingdom of living organisms, the smallest of all living organisms and therefore invisible in a light microscope, passing through the finest filters, remaining in the juice for years and at the same time not losing virulence.

So, as it was found out, viruses pass through filters that retain bacteria. They do not grow even on the most complex nutrient media and develop only in living organisms, which was considered the main criterion for distinguishing the development of viruses from other microorganisms. But bacteria were discovered that do not develop on nutrient media - rickettsia and chlamydia. Thus, a living cell is the only possible habitat for viruses, rickettsia, chlamydia and some protozoa. But now it has become clear that viruses do not need a whole cell to reproduce; they only need one specific part of it.

Modern ideas about viruses

Modern ideas about viruses developed gradually. After their discovery, they were considered simply very small microorganisms, unable to grow on artificial nutrient media. Soon after the discovery of the tobacco mosaic virus, the viral nature of foot-and-mouth disease was proven, and a few years later bacteriophages were discovered. Thus, three main groups of viruses were discovered, infecting plants, animals and bacteria.

In the late 30s and early 40s, the study of viruses advanced so much that doubts about their living nature disappeared, and in 1945 the concept of viruses as organisms was formulated. The basis for the recognition of viruses as organisms were the facts obtained during their study, which indicated that viruses, like other organisms (animals, plants, protozoa, fungi, bacteria), are capable of reproducing, have heredity and variability, adaptability to the changing conditions of their environment and, finally, susceptibility to biological evolution, brought about by natural or artificial selection.

So, having familiarized ourselves with the nature of viruses, let’s see how well they satisfy the formulated criteria for living things. Viruses are not cells and, unlike living organisms with a cellular structure, do not have cytoplasm. They do not obtain energy from food consumption. It would seem that they cannot be considered living organisms. However, at the same time, viruses exhibit the properties of living things. They are able to adapt to their environment through natural selection. This property was discovered when studying the resistance of viruses to antibiotics. Let's say that a patient with viral pneumonia is treated with some kind of antibiotic, but it is administered in an amount insufficient to destroy all viral particles. Moreover, those viral particles that turned out to be more resistant to the antibiotic and their offspring inherit this resistance. Therefore, in the future this antibiotic will not be effective.

But perhaps the main proof that viruses belong to the living world is their ability to mutate. Mutant forms are able to overcome the immunity that most people develop as a result of a previous infection. There is a widely known case of viral mutation associated with the use of the polio vaccine. This vaccine consists of a live polio virus that has been weakened so that it does not cause any symptoms in humans. In 1962, several severe cases of polio were reported, apparently caused by this vaccine. Several million were vaccinated: in some cases, a weak viral strain mutated so that it acquired a high degree of virulence. Since mutation is characteristic only of living organisms, viruses should be considered living, although they are simply organized and do not have all the properties of a living thing.

The concept of viruses as organisms reached its peak in the early 1960s, when the concept of a "virion" as a viral individual was introduced. However, during these same years, which were marked by the first successes in the molecular biology of viruses, the decline of the concept of viruses as organisms also began. Facts were summarized that pointed to a type of reproduction different from cells, emphasizing the disunity - temporal and territorial - of the synthesis of genetic material (RNA, DNA) and viral proteins. The main criterion for distinguishing viruses from other organisms was also formulated: the genetic material of viruses is one of two types of nucleic acids (RNA or DNA), while organisms have both types of nucleic acids. But the main and absolute criterion that distinguishes viruses from all other forms of life is the absence of their own protein synthesis systems (ribosomal systems).



VIRUSES

1. HISTORY OF THE DISCOVERY OF VIRUSES.

2. MORPHOLOGY OF VIRUSES.

3. VIRUS REPRODUCTION

Viruses - the smallest forms of living matter. In a certain sense, a viral particle is not a living organism, but a relatively large nucleoprotein, penetrating the cell and “multiplying” in it, forming daughter populations. These are genetic mobile elements. Outside the cell, viruses are inert, some even form crystals (for example, insect viruses form polyhedra outside the cell, consisting of protein, inside which viruses are located). All viruses exist in two qualitatively different forms - extracellular ( virion) and intracellular ( virus).

Viruses reproduce only in living cells. Selection pathogen in an infected cell culture is one of the main methods for diagnosing viral infections. Most viruses are distinguished by the presence of tissue and type specificity, for example, poliovirus reproduces only in the kidney cells of primates (poliovirus is an RNA-soda virus. The causative agent of poliomyelitis. Affects neurons of the medulla oblongata and anterior horns of the spinal cord. Paralytic form. Spinal poliomyelitis - damage to neurons of the anterior horns of the spinal cord (asymmetric damage to the lower extremities) Bulbar poliomyelitis is a lesion of the neurons of the medulla oblongata, involving the centers that control the functioning of the respiratory muscles. It is highly contagious; the infected person secretes the virus within 5 weeks. small intestine, in the lymphoid tissue of the Pirgov-Waldeyer ring and Peyer's patches; secondary viremia, the pathogen enters the central nervous system. The virus is distributed in countries of the Northern Hemisphere with a temperate climate). Influenza and measles viruses are cultured in chicken embryos. Tissue cultures are now used to diagnose many viral infections. Express diagnosis of viral infections is based on the detection of viral Ags using various serological methods - the use of antibodies labeled with fluoresceins, ELISA, RNGA, RSK, etc. Solid-phase methods (ELISA, RIA) differentially detect IgM and IgG.

If we try to arrange viruses according to their degree of complexity into a homologous series, then they, in essence, can easily fill the gap between inanimate organic matter and cellular life forms. At the very beginning of this series there will be simple minimal viruses, consisting only of protein and one type of nucleic acid (DNA or RNA). This is followed by complex viruses that also contain carbohydrates and lipids. They are followed by single-celled microorganisms - chlamydia, which, like cellular life forms, contain both types of nucleic acid and have a ribosomal apparatus.


Ivanovsky D.I. is considered the discoverer of viruses in 1892 He reported on the possibility of transfer of tobacco mosaic by the juice of diseased plants passed through Chamberlant bacterial filters. – filtering agent (virus). In 1897, Löffler and Frosch, using the principle of filterability applied by Ivanovsky, showed that foot-and-mouth disease is transmitted from one animal to another by an agent passing through filters, trapping the smallest microorganisms. Soon after this, many human and animal viruses were discovered: myxoma (Sanarelli, 1898), African horse sickness (Fadian, 1900), yellow fever (Reed and Carol, 1901), fowl sickness (Centanni, Lode and Gruber, 1901), classical swine fever (Schweinitz and Dorcet, 1903), rabies (Remlinger and Riffat-Bey, 1903), chicken leukemia (Ellerman and Bang, 1908) polio (Landsteiner and Popper, 1909). In 1911, Routh discovered a virus that causes malignant tumors in chickens. The discovery of the Rous sarcoma virus and other similar observations provided grounds for considering viruses as important factors in oncogenesis.

In 1915-1917 D´ E Rell and F. Twort described bacteriophages.Viruses were seen only with an electron microscope (the first electric microscope was designed by Ruska in 1931-1933).

Origin of viruses. Currently, there are several hypotheses explaining the origin of viruses.

1. DNA-containing bacteriophages and some DNA-containing eukaryotic viruses, possibly come from mobile elements (transposons) (mobile segments (DNA sections) capable of carrying out their own transfer (transposition) from one site to another within a chromosome or into extrachromosomal DNA (plasmid) within one cell. Some transposons (conjugative) can move to other cells in a process similar to conjugation). And plasmids .

2. Origin of some RNA viruses associated with viroids. Viroids are highly structured circular RNA fragments, replicated by cellular RNA polymerase. It is believed that viroids are "escaped introns" - cut out during splicing, insignificant sections of mRNA that accidentally acquired the ability to replicate. Viroids do not encode proteins. It is believed that the acquisition of coding regions (open reading frame) by viroids led to the appearance of the first RNA viruses. Indeed, there are known examples of viruses containing pronounced viroid-like regions (hepatitis Delta virus).

To prevent viral infection - smallpox was proposed by an English doctor E. Jenner in 1796, almost a hundred years before the discovery of viruses, the second vaccine - anti-rabies, was proposed by the founder of microbiology L. Pasteur in 1885 - seven years before the discovery of viruses.

The honor of discovering viruses belongs to our compatriot DI. Ivanovsky, who for the first time in 1892 proved the existence of a new type of pathogen using the example of tobacco mosaic disease.

As a student at St. Petersburg University, he traveled to Ukraine and Bessarabia to study the causes of tobacco disease, and then, after graduating from university, he continued his research at the Nikitsky Botanical Garden near Yalta. He found no bacteria in the contents of the affected leaf, but the sap of the diseased plant caused damage to healthy leaves. Ivanovsky filtered the juice of the diseased plant through a Chamberlant candle, the pores of which retained the smallest bacteria. As a result, he discovered that the pathogen passed even through such pores, since the filtrate continued to cause disease in tobacco leaves. Its cultivation on artificial nutrient media turned out to be impossible. DI. Ivanovsky comes to the conclusion that the pathogen has an unusual nature: it is filtered through bacterial filters and is not able to grow on artificial nutrient media. He called the new type of pathogen “filterable bacteria.”

Ivanovsky established that the tobacco disease, widespread in Crimea, is caused by a virus that is highly infectious and has a strictly defined specificity of action. This discovery showed that, along with cellular forms, there are living systems that are invisible in conventional light microscopes, passing through finely porous filters and devoid of cellular structure.

6 years later in 1898 after the discovery of D.I. Ivanovsky Dutch scientist M. Beijerinck confirmed the data obtained by the Russian scientist, coming, however, to the conclusion that the causative agent of tobacco mosaic is liquid living contagion. Ivanovsky did not agree with this conclusion. Thanks to his remarkable research, F. Leffler and P. Frosch in 1897, the viral etiology of foot-and-mouth disease was established and it was shown that the causative agent of foot-and-mouth disease also passes through bacterial filters. Ivanovsky, analyzing these data, came to the conclusion that the agents of foot-and-mouth disease and tobacco mosaic are fundamentally similar. In a dispute with M.V. Beyerinck, Ivanovsky turned out to be right.

Experiments by D.I. Ivanovsky were the basis for his dissertation “On two diseases of tobacco,” presented in 1888, and presented in a book of the same name, published in 1892 This year is considered the year of the discovery of viruses.

Subsequently, the causative agents of many viral diseases of humans, animals and plants were discovered and studied.

Ivanovsky discovered a plant virus. Leffler and Frosch discovered a virus that infects animals. Finally, in 1917 D'Herrel discovered a bacteriophage - a virus that infects bacteria. Thus, viruses cause diseases of plants, animals, and bacteria.

The word “virus” means poison; it was used by Louis Pasteur to denote an infectious principle. Later, the name “ultravirus” or “filtering virus” began to be used, then the definition was discarded, and the term “virus” took root.

In 1892, Pasteur’s contemporary and closest collaborator I.I. Mechnikov N.F. Gamaleya(1859-1949) discovered the phenomenon of spontaneous dissolution of microbes, which, as was established by D'Herelle, was caused by the action of a bacterial virus - a phage.

Under the leadership of I.I. Mechnikova N.F. Gamaleya participated in the creation of the first bacteriological station in Russia and the second Pasteur station in the world. His research is devoted to the study of infection and immunity, bacterial variability, prevention of typhus, smallpox, and other diseases.

In 1935 W. Stanley isolated tobacco mosaic virus (TMV) in crystalline form from tobacco juice infected with mosaic disease. For this he was awarded the Nobel Prize in 1946.

In 1958 R. Franklin and K. Holm, while studying the structure of the ETM, they discovered that the ETM is a hollow cylindrical formation.

In 1960 Gordon and Smith found that some plants are infected with free TMV nucleic acid, rather than the whole nucleotide particle. In the same year, a prominent Soviet scientist L.A. Zilber formulated the main provisions of the virus genetic theory.

In 1962, American scientists A. Siegel, M. Tseitlin and O. I. Zegal experimentally obtained a variant of TMV that does not have a protein shell, and found that in defective TMV particles the proteins are arranged randomly, and the nucleic acid behaves like a full-fledged virus.

In 1968 R. Shepard discovered a DNA virus.

One of the largest discoveries in virology is the discovery of most of the structures of various viruses, their genes and encoding enzymes - reverse transcriptase. The purpose of this enzyme is to catalyze the synthesis of DNA molecules on a molecule template.

In the development of virology, a major role belongs to domestic scientists: I.I. Mechnikov (1845-1916), N.F. Gamaleya (1859-1949), L.A. Zilber (1894-1966), V.M. Zhdanov (1914-1987), Z.V. Ermolyeva (1898-1979), A.A. Smorodintsev (1901-1989), M.P. Chumakov (1909-1990) and others.

In virology, several periods of development are considered.

PERIODS OF DEVELOPMENT OF VIRUSOLOGY

Rapid progress in the field of virological knowledge, based largely on the achievements of related natural sciences, has made it possible to in-depth knowledge of the nature of viruses. Like no other science, virology demonstrates a rapid and clear change in levels of knowledge - from the level of the organism to the submolecular.

The given periods of development of virology reflect those levels that were dominant for one to two decades.

Level of the organism (30-40s of the XX century).

The main experimental model is laboratory animals (white mice, rats, rabbits, hamsters, monkeys, etc.), the main first model virus was .

In the 1940s, chicken embryos were firmly established as an experimental model in virology. They were highly sensitive to influenza viruses and some others. The use of this model was made possible thanks to the research of an Australian virologist and immunologist F. Bernet, author of the first textbook on virology, “The Virus as an Organism.” In 1960 F. Burnet and P. Medawar awarded the Nobel Prize in Virology.

Discovery in 1941 by an American virologist Hurst The phenomenon of hemagglutination greatly contributed to the study of the interaction of the virus with the cell using the influenza virus model and.

The great contribution of domestic virologists to medical virology was the study of natural focal diseases -. In 1937, the first expedition was organized, headed by Zilber, which included Levkovich, Shubladze, Chumakov, Solovyov, etc. Thanks to the research, the tick-borne encephalitis virus was discovered and its carriers were identified - ixodidae, methods of laboratory diagnosis, prevention and treatment have been developed. Soviet virologists studied viral hemorrhagic diseases and developed drugs for diagnostic, treatment and prophylactic purposes.

Cell level (40-50s of the XX century).

In 1949, a significant event occurred in the history of virology - the discovery of the possibility of cultivating cells under artificial conditions. In 1952 J. Enders, T. Weller, F. Robbins received the Nobel Prize for developing a cell culture method. The use of cell culture in virology was a truly revolutionary event, which served as the basis for the isolation of numerous new viruses, their identification, cloning, and the study of their interaction with cells. It became possible to obtain cultured vaccines. This possibility has been proven using the example of a vaccine against. In collaboration with American virologists J. Salcom and A. Sabin, Soviet virologists M.P. Chumakov, A.A. Smorodintsev and others, a production technology was developed, killed and live vaccines against. In 1959, mass immunization of the child population in the USSR (about 15 million) with live polio vaccine was carried out, as a result of which the incidence of polio sharply decreased and paralytic forms of the disease practically disappeared. In 1963, for the development and implementation of live polio vaccine, M.P. Chumakov and A.A. Smorodintsev was awarded the Lenin Prize. In 1988, she decided to globally eradicate polio. This disease has not been registered in Russia since 2002.

Another important application of the virus cultivation technique was the production J. Enders and Smorodintsev live vaccine, the widespread use of which has led to a significant reduction in the incidence of measles and is the basis for the eradication of this infection.

Other culture-based vaccines were also widely introduced into practice - encephalitis, foot-and-mouth disease, rabies, etc.

Molecular level (50-60s of the XX century).

In virology, methods of molecular biology began to be widely used, and viruses, due to the simple organization of their genome, became a common model for molecular biology. Not a single discovery of molecular biology is complete without a viral model, including the genetic code, the entire mechanism of intracellular genome expression, DNA replication, information processing (maturation), etc.

In turn, the use of molecular methods in virology has made it possible to establish the principles of the structure (architecture) of viral individuals - methods of penetration of viruses into cells and their reproduction.

Submolecular level (70-80s of the XX century).

The rapid development of molecular biology opens up the possibility of studying the primary structure of nucleic acids and proteins. Methods for DNA sequencing and determination of protein amino acid sequences are emerging. The first genetic maps of the genomes of DNA viruses are being obtained.

In 1970, D. Baltimore and simultaneously G. Temin and S. Mizutani discovered reverse transcriptase in RNA-containing oncogenic viruses, an enzyme that transcribes DNA. Gene synthesis using this enzyme on a matrix isolated from polysome mRNA becomes real. It becomes possible to rewrite RNA into DNA and sequence it.

In 1972, a new branch of molecular biology emerged - genetic engineering. This year, a report by P. Berg was published in the USA on the creation of a recombinant DNA molecule, which marked the beginning of the era of genetic engineering. It becomes possible to obtain a large number of nucleic acids and proteins by introducing recombinant DNA into the genome of prokaryotes and simple eukaryotes. One of the main practical applications of the new method is the production of cheap protein preparations that are important in medicine (interferon) and agriculture (cheap protein feed for livestock).

This period is characterized by important discoveries in the field of medical virology. The study focuses on the three most widespread diseases that cause enormous damage to people's health and the national economy - cancer, hepatitis.

The causes of regularly recurring influenza pandemics have been established. Cancer viruses of animals (birds, rodents) have been studied in detail, the structure of their genome has been established, and the gene responsible for the malignant transformation of cells, the oncogene, has been identified. It has been established that hepatitis A and B are caused by different viruses: it is caused by an RNA-containing virus classified as a member of the picornavirus family, and hepatitis B is caused by a DNA-containing virus classified as a member of the hepadnavirus family. In 1976, Blumberg, while studying blood antigens among Australian aborigines, discovered the so-called Australian antigen, which he mistook for one of the blood. Later it was revealed that this is the hepatitis B antigen, carriage of which is common in all countries of the world. For the discovery of the Australian antigen, Blumberg was awarded the Nobel Prize in 1976.

Another Nobel Prize in 1976 was awarded to the American scientist K. Gajdushek, who established the viral etiology of one of the slow human infections - kuru, observed in one of the native tribes on the island of New Guinea and associated with a ritual rite - eating the infected brain of deceased relatives.

Since the second half of the 80s, virologists have been actively involved in the development of the problem of HIV infection that unexpectedly arose in the world. This was facilitated by the significant experience of domestic scientists working with retroviruses.

Medical microbiology, virology and largely owe research to domestic scientists such as N.F. Gamaleya (1859-1949), P.F. Zdrodovsky (1890-1976), L.A. Zilber (1894-1966), D.I. Ivanovsky (1864-1920), L.A. Tarasevich (1869-1927), V.D. Timakov (1904-1977), E.I. Martsinovsky (1874-1934), V.M. Zhdanov (1914-1987), Z.V. Ermolyeva (1898-1979), A.A. Smorodintsev (1901-1989), M.P. Chumakov (1909-1990), P.N. Kashkin (1902-1991), B.P. Pervushin (1895-1961) and many others.

SCIENTIFIC VIROLOGICAL INSTITUTIONS

The first virological laboratories in our country were created in the 30s: in 1930 - a laboratory for the study of plant viruses at the Ukrainian Institute of Plant Protection, in 1935 - a department of viruses at the Institute of Microbiology of the USSR Academy of Sciences, and in 1938 it was reorganized into the Department of Plant Viruses, which was headed by V.L. for many years. Ryzhkov. In 1935, the Central Virological Laboratory of the People's Commissariat of Health of the RSFSR was organized in Moscow, headed by L.A. Zilber, and in 1938 this laboratory was reorganized into the department of viruses of the All-Union Institute of Experimental Medicine, A.A. was appointed its head. Smorodintsev. In 1946, on the basis of the Department of Viruses, the Institute of Virology of the USSR Academy of Medical Sciences was created, which in 1950 was named after D.I. Ivanovsky.

During the 50s and 60s, scientific and industrial virological institutions were created in our country: Institute of Viral Encephalitis of the USSR Academy of Medical Sciences, Institute of Viral Preparations of the USSR Ministry of Health, Kiev Institute of Infectious Diseases, All-Union Research Institute of Influenza of the USSR Ministry of Health in Leningrad and a number of others.

An important role in the training of virologists was played by the organization in 1955 of the Department of Virology at the Central Institute for Advanced Training of Physicians of the USSR Ministry of Health. Departments of virology were created at the biological faculties of Moscow and Kyiv universities.

Diseases of plants, animals and humans, the viral nature of which has now been established, have caused damage to agriculture and harm to human health for many centuries.

Many of them were described a long time ago, but attempts to establish their cause and discover the causative agent remained unsuccessful. The first vaccine to prevent viral infection, smallpox, was proposed by the English physician E. Jenner in 1796, almost a hundred years before the discovery of viruses. For the first time, he realized the dream of mankind: to curb one of the most terrible human diseases - smallpox - through vaccination - an artificial inoculation of the causative agent of cowpox. The second vaccine, against rabies, was proposed by the founder of microbiology, L. Pasteur, in 1885, seven years before the discovery of viruses.

The discovery of viruses belongs to the Russian botanist D.I. Ivanovsky (1864-1920).

Using the example of tobacco mosaic disease, he proved the existence of a new type of pathogen. Studying this disease, D.I. Ivanovsky comes to the conclusion that the pathogen has an unusual nature: it is filtered through bacterial filters, retains infectious properties, is invisible under a microscope and is unable to grow on artificial media. He called the new type of pathogen “filterable bacteria.”

In February 1892, at a meeting of the Russian Academy of Sciences, D.I. Ivanovsky reported that the causative agent of tobacco mosaic disease was a filterable virus. This date is considered the birthday of virology, and D.I. Ivanovsky is its founder.

In 1897, F. Leffler and P. Frosch, using the filterability principle applied by D.I. Ivanovsky, showed that the causative agent of foot-and-mouth disease in animals is a virus. This was followed by the discovery of the causative agents of rinderpest, canine distemper, Rous sarcoma and other animal diseases. In 1915, F. Tuort and in 1917, F. d'Herelle, discovered bacterial viruses - bacteriophages. Numerous reports have appeared about the viral nature of measles, polio, influenza, encephalitis, etc.

After the discovery and development of ideas about filterable pathogens, they began to be called “ultraviruses”, later - “filterable viruses” and, finally, from the early 1940s - simply “viruses”. Thus, already in the second decade of the 20th century. viruses of plants, animals, bacteria and humans became known.

There were lulls in the flow of news about viruses, which lasted until new methods of isolating, cultivating and identifying them became available. In the 30-40s of the XX century. The main experimental model was laboratory animals sensitive to a limited number of viruses. In the 40s, virology included developing chicken embryos as an experimental model, which made it possible to discover and cultivate many new viruses: measles, infectious laryngotracheitis of birds, fowl pox, Newcastle disease, etc. The use of this model became possible thanks to the research of an Australian virologist and immunologist F. M. Burnet and American virologist A. Hershey.

A truly revolutionary event in virology is the discovery of the possibility of culturing cells under artificial conditions. In 1952, D. Enders, T. Weller, F. Robbins received the Nobel Prize for developing the cell culture method. The use of cell culture is an effective method for isolating numerous new viruses, their identification, cloning, and studying their interaction with cells.

As success was achieved in creating new research methods, the understanding of the world of viruses, their nature, the nature of interaction with sensitive cells of the body, the characteristics of antiviral immunity, the ecology of a number of viruses, their role in oncogenic processes and the evolution of a number of viral diseases of humans and animals expanded.

From the time of the discovery of viruses to the present, ideas about the nature of viruses have undergone significant changes. As the nature of viruses was studied in the first 50 years after their discovery, ideas were formed about viruses as the smallest organisms based on the presence of properties characteristic of other organisms: 1) viruses are capable of reproduction; 2) they have heredity, reproducing their own kind. The hereditary characteristics of viruses can be taken into account by the range of hosts they infect, the symptoms of diseases and the specificity of immune responses. The sum of these characteristics allows us to determine the hereditary properties of the virus; 3) viruses are variable; 4) like other organisms, they are characterized by adaptability to environmental conditions - through the host organism; 5) viruses evolve, and the driving force behind their evolution is natural selection.

Using the example of the influenza A virus, we can trace the evolution, the pace of which is measured not in millions or even thousands of years, but in a few years. Minor changes in its antigenic structure occur annually, and sudden changes in antigens occur once every 10-15 years. No other group of organisms knows such rates of natural evolution.

The main factor of natural selection in this process is artificial selection, used to breed useful breeds of animals and plant varieties. A classic example of artificial selection is the work of J1. Pasteur to obtain a vaccine strain - the fixed rabies virus, as well as the development of live vaccines against rinderpest, swine fever, polio and other diseases.

At the turn of the mid-20th century. the emergence of natural sciences at the molecular level stimulated the further development of virology, immunology, and genetics. The creation of the electron microscope brought into view the world of viruses and macromolecular compounds. The use of molecular methods in virology has made it possible to establish the structure (architecture) of viral individuals - virions (the term was introduced by the French microbiologist A. Lvov), methods of penetration of viruses into cells and their reproduction. Research has shown that the genetic substance of viruses is DNA or RNA. The nucleic acids of viruses are enclosed in a capsid case made of protein molecules; complex viruses may have outer shells (supercapsid) consisting of proteins, carbohydrates and lipids.

With the development of research into the molecular biology of viruses, facts began to accumulate that contradict the idea of ​​viruses as microorganisms due to the following unique properties:

Related to viruses are viroid agents, discovered by T. O. Diner in 1972, which cause disease in some plants and can be transmitted like ordinary infectious viruses. Viroids are relatively small RNA molecules (300-400 nucleotides) lacking a protein shell. The mechanism of viroid replication is not entirely clear.

For many years, it was believed that some slow infections in humans (Kuru, Creutzfellt-Jakob disease, Gerstmann-Streussler-Scheinker syndrome, etc.) and animals (encephalopathy in cattle, minks, etc.) are caused by viruses. However, it turned out that the cause of these diseases is a new pathogenic agent - a prion, discovered in the early 80s of the 20th century. American biochemist Stanley Prusiner.

Despite the many years of development of the study of viruses, there is still no generally accepted definition of them. The definition of “viruses” is somewhat arbitrary, and many variations have been proposed at different times.

Viruses are non-cellular life forms. Apparently, viruses can be considered as biological entities that carry genetic information, which they implement only in living cells of humans, animals and plants.

Various assumptions have been made about the origin of viruses. Some authors believe that viruses are the result of an extreme manifestation of the regressive evolution of bacteria and other single-celled organisms. Most virologists do not share this hypothesis.

According to the second hypothesis, viruses are descendants of ancient, precellular life forms. Most researchers also do not share this hypothesis.

The hypothesis of the endogenous origin of viruses is supported by the largest number of virologists. She suggests that viruses originated from genetic elements of cells (“run amok”) that became autonomous. Viruses probably arose and evolved along with the emergence and evolution of cellular life forms.

The importance of viruses in our lives is very great. On the one hand, these are the etiological agents of most infectious diseases of humans, animals and plants; on the other hand, viruses, due to the relative simplicity of their structure, are an excellent biological model for solving fundamental problems of biology, genetics, biochemistry, immunology, and genetic engineering. “Viruses provide us with the only key to understanding the function of nucleic acids, and perhaps to understanding the nature of life itself.”

In 1974, V. M. Zhdanov put forward a hypothesis according to which viruses are an important factor in the evolution of the organic world. Overcoming species barriers, viruses can transfer individual genes or groups of them, and the integration of viral DNA with cell chromosomes can lead to the fact that viral genes become cellular genes that perform important functions.

Why has virology, which originated in the depths of microbiology, achieved such rapid success in recent years, becoming one of the leading and core disciplines of biomedical and veterinary sciences? A number of circumstances contributed to this.

Firstly, as the role of bacteria, protozoa and fungi in infectious pathologies of humans and animals, for the treatment and prevention of which there are reliable biological and chemotherapeutic drugs, has decreased, the role of viruses has increased. Neither medical nor veterinary science has yet created such drugs against many viral diseases. Thus, problems with diseases such as influenza, rabies, foot-and-mouth disease, etc. have not yet been resolved.

Secondly, the possibility of using viruses as a biological model. Thus, many fundamental discoveries in the field of biology were made thanks to viruses (the mechanism of DNA replication, the mechanism of protein synthesis, etc.).

Thirdly, it has been established that in widespread respiratory intestinal diseases of young animals, causing enormous economic damage, viruses from various taxonomic groups (adeno-, rota-, corona-, paramyxoviruses, diarrhea viruses, etc.) play a major role. It turned out that when outbreaks of these diseases occur, various viruses, bacteria, chlamydia and stress factors closely interact.

Fourthly, certain types of pathology (congenital deformities, developmental defects, etc.), where the role of viruses was not even suspected, turned out to be virological. It is known in medicine that viruses are one of the causes of intrauterine human pathology (rubella virus, influenza virus, adenoviruses, etc.). Unfortunately, this problem has not received due attention in veterinary virology. Although the teratogenic effect of viruses is also observed in the infectious pathology of animals: swine fever virus often causes stillbirth and mummification of fetuses; bovine diarrhea virus - cerebellar hypoplasia of newborn calves; chicken infectious bronchitis virus - pathological form of eggs; Infectious rhinotracheitis virus - developmental defects, blindness in calves.

The role of viruses in the occurrence of some chronic diseases has been established. Information is accumulating on the role of viruses in acute cardiovascular diseases, diseases of the kidneys, pancreas, eyes, etc. Only comprehensive studies can serve as the basis for judging the role of viruses in diseases of unclear etiology, which are still being studied by non-infectious disease doctors.

The fact of migration of human strains of the influenza virus into the animal world is very important from both an epidemiological and epizootological point of view. Influenza viruses evade the body's immune system by rapidly changing their antigenic determinants. This makes it difficult to implement timely, effective, specific prevention methods. Unfortunately, the problem of influenza is still very relevant.

And finally, indisputable evidence has accumulated that many tumor diseases are caused by viruses (leukemia of birds, cattle, Marek's disease, etc.). Finding out the causes of human malignant diseases, which kill millions of people around the world every day, remains one of the most important problems of modern biology and medicine.

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