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oncogenic virus[¦aŋ·kə‚jen·ik ′vī·rəs]
(also tumorigenic, or tumor, virus), the causative agent of certain benign and malignant tumors in animals and, apparently, in man. Successful experiments to induce tumors in animals using filterable agents, or viruses, were performed early in the 20th century, but the study of oncogenic viruses was not established as an independent scientific discipline until the 1950’s and 1960’s. Progress in studying oncogenic viruses is closely associated with the rise of molecular biology.
Oncogenic viruses differ from each other in several important respects: (1) in the type of nucleic acid that they contain, that is, ribonucleic acid (RNA) or deoxyribonucleic acid (DNA); (2) in morphology, for example, in the shape, size, and type of symmetry of the virions and in the presence or absence of an outer membrane; (3) in the site of virus reproduction in the host cell, which can either be in the cytoplasm or in the nucleus; (4) in the mode of transmission of the virus, which can be vertical —from parents to offspring and from cell to daughter cell—or horizontal—from individual to adjacent individual and from cell to adjacent cell; and (5) in virulence.
Some DNA viruses initiate uncontrolled cell reproduction in some cell systems and an infectious process that usually causes cell destruction in others. Therefore, in the words of L. A. Zil’ber, with respect to DNA viruses “one should not speak of tumor and infective viruses but of the neoplastic and infective action of viruses.”
RNA viruses are more easily classified as oncogenic or infective, that is, they usually induce either tumors or infectious processes. The oncogenic RNA viruses also differ from most infective RNA viruses in that they produce nucleic acid according to the scheme RNA → DNA → RNA, while infective RNA viruses produce nucleic acid according to the scheme RNA(+)→ RNA(–)→ RNA(+). The ability of oncogenic RNA viruses to synthesize virus-specific DNA on their own RNA matrix (a process called reverse transcription) and to exist, therefore, in two forms—that of a complete virus (RNA plus protein) and that of a DNA provirus—was demonstrated in 1970 by the American researchers H. Temin and S. Mizutani. Another American, D. Baltimore, independently achieved the same results in that year. The discovery of the DNA form in RNA oncogenic viruses strongly supported Zilber’s viral-genetic theory, whereby a cell becomes a tumor cell through the combination of the cellular genome with the genome of an oncogenic virus.
During the second half of the 1960’s, it was experimentally confirmed that the chromosomes of non-virus-producing tumor cells that had been transformed by DNA viruses contain the genomes of these oncogenic viruses; these oncogenic genomes were synthesizing virus-specific messenger RNA. By the end of the 1960’s it was found that the genetic information in oncogenic RNA viruses that appear to be in the DNA provirus form is present not only in tumor cells but also in all normal vertebrate cells that were studied. Relying on these findings, R. Huebner and G. Todaro in the United States hypothesized that the various oncogenic agents, including chemical carcinogens, radiation, normal aging processes, and exogenous viruses, all act by a single mechanism: they activate the endogenous oncogenic information that is present in a “repressed” state in all cells.
In response to oncogenic agents and sometimes after prolonged breeding, many cells begin to release particles that are similar to oncogenic RNA viruses with respect to several features, including morphology and physical chemistry. However, these particles, in contrast to the oncogenic RNA viruses that are released from tumor cells, are completely or almost completely nononcogenic. According to Temin, normal cells do not contain oncogenic information: aberrant RNA or DNA molecules that are transcribed from initially nononcogenic DNA originals, or “protoviruses,” randomly acquire their oncogenic properties. Temin suggests that malignant transformation takes place when such aberrant DNA copies are incorporated into the genome of the original cell or of a neighboring cell.
In the 1960’s and 1970’s, viral particles that are similar to the causative agents of tumors and leukoses in birds and mice were found in human neoplasms and in continuously cultured tumorous and normal human tissues. The possible significance of these viruses as specific causative agents of tumors and leukoses in man is now under study.
REFERENCESZil’ber, L. A. Viruso-geneticheskaia teoriia vozniknoveniia opukholei. Moscow, 1968.
Kiselev, L. L. “Viruso-geneticheskaia kontseptsiia vozniknoveniia opukholei (eksperimental’nye dokazetel’stva).” Voprosy virusologii, 1970, no. 2.
“K izucheniiu onkornavirusov.” Voprosy virusologii, 1973, no. 1.
Huebner, R. J., and G. J. Todaro. “Oncogenes of RNA Tumor Viruses as Determinants of Cancer.” Proceedings of the National Academy of Sciences (USA), 1969, vol. 64, no. 3.
Temin, H. M. “RNA-directed DNA Synthesis.” Scientific American, 1972, vol. 226, no. 1.
G. B. GOKHLERNER