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Oncogenic viruses

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Among the factors that most reliably contribute to the transformation of a proto-oncogene into an oncogene are some viruses. For the first time these particles, located on the border of the living and nonliving, were discovered in 1892 by a graduate of St. Petersburg University, DI Ivanovsky.

In 1907, the French researcher A. Borel put forward a hypothesis about the connection of cancer with viruses. Such a relationship was first shown in 1908, when Danish scientists Ellerman and Bang found that in chickens, the causative agent of leukemia can be repeatedly passed through bacterial filters and does not lose its aggressiveness. In 1910, American Peyton Routh established a link between viruses and chicken sarcoma. In 1934, his compatriot R. Shoup isolated a virus from a tumor of warts, or papillomas, of rabbits. In 1936 G. Bittner discovered the breast cancer virus of mice, and in 1951 L. Gross - the virus of leukemia of mice, in 1964 V. Jarrett - the virus of leukemia of domestic cats, and then the virus of leukemia of monkeys. Soviet scientists under the leadership of Academician of the USSR Academy of Medical Sciences B. A. Lapin made a great contribution to the study of the latter. Today, more than 100 viruses that cause tumors in animals and therefore called oncogenic are known.


A study of leukemia viruses in chickens, mice and cats showed their significant chemical and antigenic commonness, and electron microscopy confirmed the similarity of their structure. In most cases, under natural conditions, viruses can cause tumors only in "their" animal species. The mouse leukemia virus does not infect leukocytes in cats, and vice versa. Cats become ill with leukemia, catching from each other, just as we catch the flu (horizontal transmission). But in mice, even prolonged contact with diseased animals is safe for healthy animals. The spread of the virus occurs from parents to offspring (vertical transmission). In chickens, the disease can be transmitted in both ways. In 1957, Soviet researchers (L. A. Zilber with co-workers and simultaneously G. Ya. Svet-Moldavsky with co-workers) proved that species specificity is not a strict property of oncoviruses: the chicken sarcoma virus can also cause tumors in rats.

Then, in 1958, the distinguished Soviet immunologist and virologist L. A. Zilber formulated the main provisions of the viral theory of cancer. According to her, the virus does not cause destruction of the cell, but introduces its hereditary information into it, which becomes an integral part of the genome of animal cells. An infected cell does not immediately turn into a cancer cell, although a number of its biological parameters already differ from healthy cells. For oncogenesis, some kind of activating factor is needed to stimulate the reproduction of virus-infected cells. Zilber said that the virus "needs special conditions in order for it to show disease, but as long as there are no conditions, the virus is completely harmless." As can be seen, the Zilber hypothesis was further factually confirmed, although the “starting pistol”, giving the signal for the accelerated reproduction of infected cells, has not yet been found.

In all living biological objects, genetic information is stored in DNA, and from there RNA is transmitted through the transcription process. Later in the course of translation, this information is transformed for the subsequent protein synthesis in the cytoplasm on the ribosomes. For some viruses, everything happens the other way round: their genetic information is written in RNA, and already in the cell that has become a refuge for viruses, a new DNA is built in the process of reverse transcription using enzymes (reverse revertase). Such viruses are now called retroviruses or RNA viruses.


Among the viruses that cause infectious diseases, there are DNA viruses (smallpox, herpes) and RNA viruses (influenza, rabies, polio, measles). DNA viruses (often causative agents of tumors in monkeys, fibromas in rabbits), and RNA viruses ( breast cancer in mice, viruses of leukemia in cats and mice, and causative agents of sarcoma) can also be oncogenic.

The virus penetrates only those cells that have receptors for it. The sensitivity of viruses to certain molecules of a narrow group of cells, such as T-helper cells, and only to them is amazing. In some cells, the virus multiplies, in others - not. In cells that allow the reproduction of the virus, the number of its particles increases to tens of millions, and in the end they break the cell membrane. In other cases, the virus does not multiply, but rather “sticks” to the cell receptors, then penetrates the membrane and begins to synthesize viral proteins using its informational (or matrix) RNA molecules. This is not hampered by the fact that cellular enzymes destroy the own protein shell of the virus, the main thing is that its nucleic acid is preserved.

This latter is then firmly inserted into the cell’s DNA (“integration” of the virus). Now, along with the usual set of proteins that are displayed on the cell membrane, its DNA gives orders about the development of a new antigen, viral. Another option: a viral antigen replaces one of the class I tissue compatibility proteins or causes them to cluster and not properly positioned on the membrane. In any case, the cell must be recognized by EC-cells of immune surveillance or T-lymphocytes. But if the viral protein has immunosuppressive properties, such a slight change in the surface of the virus-transformed cells can be overlooked by the lymphocytes.