ONCOGENOUS VIRUSES

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ONCOGENOUS VIRUSES (Greek onkos the weight, a tumor + gennao to create, make; viruses: synonym onkovirusa) — group of viruses, obladayushchmkh ability to cause transformation of normal cells of eukaryotes in tumoral. A. Borel and F. J. Bose, Ellermann and Bang (V. Ellermann, O. of Bang, 1908) were the first researchers who introduced in 1903 the idea that tumors, in particular cancer, can be caused by agents of the virus nature. A bit later Raus (1911) in an experiment established a virus etiology of a leukosis and sarcoma of hens. However these works long did not find recognition especially as at that time leukoses did not consider neoplastic diseases. Only in 1966 F. Raus was conferred the Nobel Prize for fundamental researches in the field of an onkovirusologiya.

The idea about a role of viruses in developing of tumors long since occupied minds of the Russian scientists. I. I. Mechnikov in 1909 publicly declared: «Very possibly..., that cancer diseases of the person are obliged by the origin to some virus, to-ry diligent look for, but did not find yet». Developing a thought of participation of viruses in developing of tumors, I. I. Mechnikov in 1910 claimed that only one penetration of viruses into an organism is not enough for development of cancer and that they can show the pathogenesity only under the corresponding conditions, the basic from to-rykh it considered availability of chronically struck fabrics.

Long time of attempt to allocate a virus, to-ry causes tumors in mammals, remained ineffectual. Moreover, the fact of receiving tumors at hens as a result of administration of various chemical substances called cancerogenic by it was capable to shake opinion on wildlife of the activator and on its belonging to viruses. Nevertheless even those years wrote (1930 — 1931) N. F. Gamaley: «... if cells of sarcoma can arise in an organism of chicken or in fabric cultures without introduction of a virus, and under the influence of sterile substances..., it is necessary to assume that the sarkomatozny virus predsushchestvut in latent healthy sections., without showing the presence..., does not interfere them with normal life and has no independent metabolism since does not change them to assimilation». This situation allows to consider that N. f. Gamaley the first predicted existence and value of endogenous onkovirus.

Only in 1932 — 1933 R. Shoup described viral tumors at mammals — fibroma and papilloma of wild rabbits, from to-rykh the last could regenerate in a carcinoma. Then J. Bittner described a virus of cancer of mammary glands of mice in 1936, and in 1951 Lgross reported about allocation of a virus of a leukosis of mice. The researches conducted in the different countries showed that O.'s number of century is quite high and makes more than 200. Among O. century there are both DNA - and the RNA-containing viruses.

RNA-containing O. of century (oncornaviruses) represent the most numerous group of the viruses which are an origin of malignant new growths at feral hosts (see. Retrovirusa ). DNA-containing O. of century divide into three groups: viruses of papillomas (see. Papova viruses ), viruses of group of herpes (see. Herpes viruses ) and viruses of group of smallpox (see. Poksvirusa ), to-rye have property to cause various tumors. Among O. century there are viruses causing tumors practically in all representatives of fauna (see the tab.). Only identification of RNA-containing O. of century in tumors of the person still remains unspecified.

Fig. 1. Diagrammatic representation of onkovirus. The RNA-containing onkovirusa (1 — 4): 1 — onkovirus type A, 2 — onkovirus type B, 3 — onkovirus type C, 4 — onkovirus type D; The DNA-containing onkovirusa (5 — 8): 5 — onkovirus groups of smallpox, 6 — onkovirus groups of herpes, 7 — adenovirus, 8 — a Papova virus.

On morphology of RNA-containing O. of century divide into onkovirusa (or retroviruses) type A, B, C and D (fig. 1,7 — 4). Lakes of century of type A are considered by hl. obr. as intracellular predecessors of O. of century of types B, SI D. Assume also that among O. century of type A there is an independent group of viruses, the role to-rykh is unknown. Lakes of century of type B are activators of carcinomas of mammary glands at mice, and O. century of type C — leukoses and sarcomas at birds and mammals; Lakes of century like D combine a virus of monkeys of Meyzon — Pfayzera, a virus of the intertwined cancer cells of the person, endogenous viruses of squirrels and monkeys.

Fig. 2. Diffraction patterns of extracellular DNA-containing of onkovirus: and — a virus of a contagious mollusk (negative contrasting, x 100 000); — herpes virus of type 2 persons (ultrathin section, X 100 000), 1 — a viral envelope, 2 — a core of a virus; in — the site of a surface of a capsid of a gerpesvirus of type 2, shooters designated separate capsomeres (positive contrasting, X 600 000); — a virus of papilloma of the person, shooters designated capsomeres (negative contrasting, X 300 000).

The structure and morphogenesis of DNA-containing O. of century are various and similar to the submicroscopic organization and intracellular development inf. viruses of group of smallpox, herpes, adenoviruses, Papova viruses (fig. 1, 5—8 and fig. 2).

Fig. 3. The diagrammatic representation of structure of the RNA-containing onkovirus of type C: 1 — a core of a virus; 2 — a cover: 3 — a head of a shoot of a cover; 4 — a thorn of a shoot of a cover; 5 — an inner (subshell) layer; 6 — the capsule of a core of a virus; 7 — molecules of a revertaza; 8 — molecules RNA; 9 — nucleoid of a virus.
Fig. 4. Diffraction patterns of extracellular RNA-containing of onkovirus (negative contrasting): and — onkovirus type A; 6 — onkovirus type C (a virus of sarcoma of woolly monkeys); in — onkovirus type B (a virus of cancer of mammary glands of mice); — onkovirus type D (a virus of the intertwined cells of throat cancer of the person); 1 — a viral envelope, 2 — a core of a virus; X 120 000.

The RNA-containing O. extracellular virions of century consist of the cover and a core having rather complex structure as, e.g., at O. century of type From mammals (fig. 3 — 4). Two main signs are characteristic of intracellular development of RNA-containing O. of century: integration of a virus DNA transcript (DNK-ovoy copies of the virus RNA-containing genome, edges it is synthesized by virus enzyme — revertazy) with a genome of a cell and existence of an additional stage of a differentiation (maturing) at allocated (or allocated) from O.'s cell of century (tsvetn. fig.).

Fig. 5. Diffraction patterns of a surface of a cell with the budding RNA-containing onkovirusa: and — formation of usual forms of an oncogenous virus (it is specified by shooters) type From a leukosis of mice (ultrathin section); — formation of the minimum form of an onkovirus of the C (1) type and usual extracellular onkovirus of the C (2) type — ultrathin section; in — an extracellular minimum form of an onkovirus of type A (negative contrasting); — an extracellular minimum form of an onkovirus of type C (ultrathin section, X 100 000).

In addition to usual RNA-containing of oncogenous viruses (fig. 5, a), described the RNA-containing O. so-called minimum forms of century (fig. 5, in, d), to-rye are found in population of onkovirus of type A, C and D. They differ in smaller size and form or on a surface of a cell, or in the course of fragmentation of extracellular onkovirus under unfavorable conditions of cultivation. In similar conditions numerous abnormal forms of onkovirus, in particular their huge forms (fig. 6) come to light.

Fig. 6. Diffraction patterns of huge forms of oncogenous RNA-containing of viruses: and — budding of huge forms of an onkovirus of type A (1 — huge onkovirus, 2 — budding usual onkovirus, 3 — a cell membrane); — on the right — an extracellular huge form of an onkovirus of type C (3 — a viral envelope, 2 — a core of a virus); at the left — usual onkovirus type C (ultrathin cuts, X 70 000).

The big role in formation of a modern onkovirusologiya belongs to the Soviet scientist L. A. Zilber who for the first time stated a hypothesis of a possibility of integrative interaction of tumoral viruses and cells, edges afterwards gained full and universal recognition as the viruso-genetic theory of developing of tumors (L. A. Zilber, 1968).

In process of accumulation of data there was the following scheme of the mechanism of virus carcinogenesis. Virus genetic material is fixed in a cell, becomes a component of a cellular genome. As a part of the fixed virus genome is available a gene (genes), the product to-rogo directly is responsible for transformation of a normal cell in tumoral (such genes received the name of oncogenes). The product of an oncogene («cancer protein») which is formed as a result of functioning of an oncogene with firmness breaks normal regulation of cellular division — the cell becomes tumoral. As for volumetric and physical cancerogenic factors, they increase activity till that time of the viruses which were not showing the tumoral nature.

Strengthening of oncogenic properties O. of century at infection of animals not - oncogenous viruses was for the first time described by the Soviet virologist N. P. Mazurenko in 1957 — 1962 and received the name of a virusnovirusny kokantserogenez (see. Carcinogenesis ).

In addition to RNA-containing O. of the century getting to a cell from the outside so-called endogenous onkovirusa, genetic information are found to-rykh contains in a genome of all cells of this species of animals (including and in a genome of sex cells). Cells of natural owners of all known endogenous viruses are adverse for reproduction of these viruses. The role of endogenous onkovirus is unknown. The Soviet virologists V. M. Zhdanov and T. I. Tikhonenko suggested that these endogenous onkovirusa can be one of factors of a cellular differentiation and exchange of genetic information in the biosphere.

See also Viruses .

Fig. is represented. An intracellular development cycle oncogenous RNA - the containing virus (onkovirus). In the drawing the cell in which oncogenous RNA-viruliferous passes an intracellular cycle of reproduction is represented: 1 — extracellular onkovirus type C; 2 — adsorption and penetration of virion of an onkovirus of type C into a cell; 3 — deproteinization ("undressing") of virion; 4 — the transkriptivny complex providing formation one-and two-spiral virus DNA (1), DNA (2) on a matrix of RNA of a virus; 5 — linear two-spiral DNA of a virus; 6 — the ring form of virus DNA formed of linear DNA of a virus; 7 — penetration of a ring form of virus DNA into a kernel of a cell; 8 — integration of virus DNA into a genome of a cell; 9 — synthesis of virus RNA; 10 — transition of virus RNA from a kernel of a cell in cytoplasm and inclusion in structure of the polyribosome which is localized on a membrane of a granular endoplasmic reticulum; 11 — synthesis of virus glycoproteins — gp (gp15e and gp70); 12 — transport of virus glycoproteins to a surface of a cell; 13 — localization of virus glycoproteins on a plasmatic cell membrane; 14 — transition of virus RNA from a kernel in cytoplasm and inclusion in structure of the linear polyribosome synthesizing proteins of a virus core (15), 16 — transport of the new synthesized proteins (p10, PZO, p12, p15) to a surface of a cell; 17 — transition of virus RNA from a kernel in cytoplasm and inclusion in structure of the linear polyribosome synthesizing a revertaza (18); 19 — transport of a virus revertaza to a surface of a cell; 20 — transport of a virus ribonucleoprotein to a surface of a cell; 21 — assembly of a core of an onkovirus; 22 — formation of an onkovirus from separate virus components [glycoproteins (1 1—13), proteins of a core (15, 16) and revertaza (18, 7R)] in the course of budding on a surface of a cell; 23 — transformation of an extracellular onkovirus of the type A containing spherical nucleoid in onkovirus type C with dense nucleoid (24)

Table. Oncogenous viruses of vertebrata and diseases caused by them (or detection of a virus)

Bibliography: G. I., etc. is Abelian. Tumoral growth as problem of developmental biology, M., 1979; Ageenko A. I. Mechanism virus ©нкогенеза, M., 1978; The Atlas of virus cytopathology, under the editorship of B. M. Zhdanov, M., 1975; Bykovsky A. F. and Klitsunova of N. B. Stroyeniye of unusual («minimum») forms of oncornaviruses of type A and C, Dokl. Academy of Sciences of the USSR, t. 224, No. 1, page 226, 1975; Zhdanov V. M., Bykovsky A. F. and Ilyin K. V. Oncogenous viruses of D type, M., 1979; 3 and l-ber JI. And., etc. Evolution of the virusogenetichesky theory of developing of tumors, M., 1975; B. A. Wingnuts, etc. Hemoblastoses of primacies and a role of viruses in their emergence, M., 1979.


I. G. Balangding, A. F. Bykovsky.

Яндекс.Метрика