RETROVIRUSES (Retroviridae) - the family of viruses, for to-rykh is the combining sign existence in structure of virions of a revertaza (the return transcriptase) — the enzyme synthesizing DNA on a matrix of RNA of a virus.
For the first time R. were described in 1908 by Ellermannom and Bang (V. Ellermann, O. Bang) studying activators eritro-and myeloblastoses of birds. Later F. Raus (1911) described the virus of sarcoma of hens which received the name a virus of sarcoma of Raus. On classification of 1970 these and other similar viruses were united in a sort of leykovirus (Leukovirus; Greek leukos white, i.e. the viruses causing a malignant leukemia, leukoses). In 1975 these viruses were included in classification of viruses as oncornaviruses [Greek oncos a tumor + RNA (English ribonucleic acid) — the tumoral RNA-containing viruses]. However these names long did not exist as, on the one hand, viruses entered into group of these viruses, not only the causing leukoses but also leading to development of sarcomas and tumors of a mammary gland, and with another — were included in this group viruses, not obladashchy by oncogenous properties, but containing a revertaza. Existence of the revertaza providing retro return (Latin, characteristic of such viruses, back) a flow of information (from RNA to DNA), also formed the basis for formation of the name of this family — Retroviridae including subfamilies of onkovirus, spumavirus and lentiviruses (tab).
Viruses of a subfamily of onkovirus (Oncovirinae) are the most studied. The round form is inherent in them, diameter does not exceed 100 nanometers, and floating density makes 1,15 — 1,19 g/cm 3 . Onkovirusa contain RNA, edges it is presented by two aggregated identical 35 S-molecules consisting approximately of 10 000 nucleotides, a pier. the weight (weight) of each molecule makes apprx. 3*10 6 dalton, they are connected among themselves by hydrogen bindings in the area 5' - the ends. Except this high-molecular RNA which is usually called 70 S-PHK as a part of virions also low-molecular RNA (4 — 5 S) representing cellular sPHK or GRNK come to light. In total RNA structurally are a part of nucleoid (floating density of 1,26 — 1,31 g/cm 3 ), coated. This education which received the name of a core of virion (floating density of 1,21 — 1,23 g/cm 3 ), it is surrounded with the external cover having shoots and consisting of external and internal membranes. Morphological structures at onkovirus have certain rodospetsifichesky distinctions (see fig. to St. Oncogenous viruses ). So, at onkovirus With a core large it is also located it is central, at onkovirus In and the D core is located excentricly; nucleoid at onkovirus In round, and at onkovirus of D — cylindrical. Shoots at onkovirus In and With long, and at onkovirus of D and a subgenus of onkovirus From mammals — short.
In addition to onkovirus And yes From the usual sizes, also their minimum forms, the sizes to-rykh apprx. 30 — 40 nanometers are described. The minimum forms contain all proteins inherent in virions of the normal sizes, but considerably smaller on molecular sizes of RNA.
Chemical structure of onkovirus following: RNA — apprx. 1 — 2%, a squirrel (5 — 8 various polypeptides) — 60 — 70%, lipids — 30 — 40% and carbohydrates — apprx. 1 — 2%. The main component of a cover — a glycoprotein (500 — 1000 molecules in one virion) about a pier. weighing 50 — 80 kilodalton; the second glycoprotein has a pier. weight 22—45 kilodalton. There are also neglikozilirovanny proteins about a pier. weighing 15 and 12 kilodalton. As a part of a core secrete the main internal protein (a pier. weight 24 — 36 kilodalton) and additional proteins, among to-rykh a revertaz (10 — 20 molecules in virion) and other enzymes (DNA-ligase, a DNA polymerase, ekzo-and endonucleases, RNK-metilaza, etc.). The viruses relating to one look have identical (or relatives) the main internal proteins called group-specific antigen (gs-antigen); the subspecies which are a part of one look differ on antigenic properties of coat proteins or separate additional internal proteins. In subspecies there can also be certain options.
RNA of onkovirus — the carrier of genetic properties of virion. In it distinguish the genes coding synthesis of outside proteins (a gene of env), revertaza (a gene of pol), internal proteins (a gene of gag) and the genes responsible for transformation of the infected cells (a gene of src). Loss of a gene of src does not influence ability of viruses to be reproduced in cells, then, as loss of any of three other genes does a virus defective, needing a virus assistant.
In vitro onkovirusa cultivate on animals, for to-rykh they possess an oncogenous potentiality, and in cells both primary, and intertwined cellular cultures. The cycle of a reproduction of onkovirus in cells consists of two phases. The first phase begins with adsorption and penetration of a virus into a cell — the processes not different from similar processes at any viruses (see). It comes to the end characteristic for oncogenous viruses (see) integration with cellular genome DNK-provirusa, i.e. DNA, edges was synthesized by revertazy; on a matrix of onkovirusny RNA, In a result in the genome of one infected cell can be built in from one to five DNK-provirusa, the Second phase consists in the expression integrated DNK-provirusa, edges, however, does not begin until the infected cells pass a stage of a mitosis. As a result of expression DNK-provirusa RNA of onkovirus, then proteins of viruses and, at last, an onkovirusa are formed. The final stage in formation of onkovirus is an exit of their news agency of a cell, in process to-rogo the synthesized core of a virus contacts an inner surface of the changed site of a plasma membrane of a cell and in process of escaping of the last is surrounded with this membrane.
Onkovirusa do not cause death of cells: infection with them has chronic character. The reproduction of onkovirus is followed by antigen conversion of cells as on a plasma membrane of cells noncellular polypeptides — products of genes of env and gag appear. In case of existence in a genome of an onkovirus of a gene of src in cells so-called cancer protein is synthesized, to-ry causes transformation of a cell in tumoral (cancer).
Cells can receive a genome of onkovirus in the hereditary way (a vertical way of transfer). In this case all posterity of the individual containing in the genome DNK-provi-rusa will also contain in the DNA information for synthesis of onkovirus. At the same time it is not obligatory that in case of inheritance inevitable implementation of information concluded in them happened cells of onkovirusny genomes. That such implementation took place, impact on these cells of the certain chemical connections known under the name of carcinogens is necessary. Also spontaneous induction of synthesis of onkovirus is possible, however.
For identification of onkovirus in fabrics (cells) there is a number of the methods which are mutually confirming to each other. Methods of electronic microscopic examinations are widely applied to detection in cells of the onkovirus possessing specific structure. Also methods physicochemical and biochemical (detection of the virus particles with a characteristic floating density containing 70 S — RNA and a revertaza), immunological (identification in cells of antigens, specific to onkovirus) and biological are used (establishment in animal experiments or with cellular cultures of specific biological effect).
Onkovirusa are eurysynusic at animals, and for many of them the role of an etiological factor in developing of tumors is proved (e.g., a virus of cancer of mammary glands of mice, a virus of sarcoma of birds etc.). Many researchers divide Hübner and Todaro's hypothesis (R. J. Huebner, G. J. Todaro) formulated in 1969 that at the person (as well as at animals) malignant tumors can result from activation of the inherited genomes of retroviruses. However at the person such onkovirusa are not revealed. Detection in the intertwined tumor cells of the person of onkovirus, in particular similar by the fact that caused a breast cancer at monkeys most of virologists consider only laboratory viruses-game-taminantami. One of eurysynusic arguments against an etiological role of onkovirus in pathology of the person it is considered to be that fact of common knowledge that malignant tumors of the person are not infectious.
Spumavirusa (Spumavirinae; English spume foam), or foaming viruses, syncytial, simplastoobrazuyushchy viruses — the subfamily combining group of viruses to-rye at infection of epithelial and fibroblastny cells cause merge of these cells to formation of the sincytia containing up to 100 and more kernels and emergence in cytoplasm of numerous vacuoles that reminds foam. Under a supermicroscope of a spumavirusa (fig. 1) are similar to virions of onkovirus of A. Spumavirusa are allocated from monkeys, cats, hamsters, cattle and the person; cause persistent asymptomatic infections in feral hosts and experimental animals. Spumavirusa as in the respiratory way (a horizontal way of transfer), and in a hereditary way extend. Ability to an opukholeobra-zovaniye or transformation of cells, as well as pathogenicity at these viruses, are not established. For the infectious process caused by spumavprusa slow development is peculiar: from the moment of infection before identification of characteristic specific changes in cytoplasm of cells there pass several weeks. The extracellular virus is not found; its distribution comes directly from a cell in a cell.
Lentiviruses (Lentivirinae; lat. lentus slow) — R.'s subfamily combining group of viruses characteristic feature to-rykh is slow development of the infectious process caused by them (see. Slow viral infections ). Lentiviruses are under natural conditions allocated only from sheep. Viruses of a visn (fig. 2), Mady and the progressing pneumonia of sheep concern to them. Morphologically they remind onkovirusa With, breed in cultures of cells of sheep, causing a simplastoobrazovaniye. There are instructions on ability of a virus of a visn to cause transformation of cells, however tumors do not induce these viruses. In the antigenic relation lentiviruses are close that the nek-eye to researchers gives the grounds to consider them as options of the same virus.
Mady's virus causes after long (2 — 3 years) an incubation interval slowly progressing chronic intersticial pneumonia which is coming to an end with death of animals a year later after emergence of symptoms of a disease. During the opening of the fallen sheep lymphocytic diffusion perivascular and peribronchial infiltration, diffusion proliferation of a mesenchyma, increase in peribronchial, tracheobronchial and mediastinal lymph nodes is found in them, changes of willows of c are noted. N of page. In an experiment Mady's virus possible to infect rabbits, Guinea pigs and mice; in addition to cells of sheep, Mady's virus can be cultivated in cells of kidneys of embryos of cows and adrenal glands of hamsters.
The virus of a visn causes a demyelinating disease of certain breeds of the sheep divorced in Iceland. After an incubation interval duration up to 4 years notes symptoms of defeat of c. N of page: constraint, lameness, a side deviation of the head, then come paresis and paralyzes. The disease lasts about a month, all sick sheep perish. Pathoanatomical changes are characterized by symptoms of diffusion encephalitis with demyelination. At intra pulmonary infection of sheep with a virus of a visn the same changes are noted, as at Mady's disease.
The progressing pneumonia of sheep for the first time was described in Iceland, but then was observed in France, Holland, South Africa. The incubation interval can proceed up to 3 years. Symptoms of a disease are similar with observed at Mady's disease, however the pathoanatomical picture is a little other than that at Mady. In 3 — 12 months after emergence of the first symptoms of a disease death of animals is caused by disturbance of breath.
See also Cancer of mammary glands viruses .
Table. CLASSIFICATION of VIRUSES of FAMILY of RETROVIRUSES (RETROVIRIDAE) of ANIMALS
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