Retroviruses and Cancer

Retroviruses are among several types of viruses that can induce cancer in the host organism. So-called slowly transforming viruses are exemplified by human T-lymphotropic virus (HTLV), which causes leukemia (a type of blood cancer) in humans. These viruses induce malignancy by a process called insertional mutagenesis. The initial event is thought to be retroviral integration near, and subsequent activation of, a cellular oncogene (c-onc). Examples of c-onc include genes for growth factors, protein kinases, and transcription factors. Harold Varmus and Michael Bishop won the Nobel Prize for physiology or medicine in 1989 for their contributions to the discovery of oncogenes.

When a malignancy is triggered, tumors appear only after a long latent period of months or years, and these tumors are typically clonal in origin. That is, they arise by the rare transformation of a single cell. HTLV-1 is highly prevalent in people living in Japan, the Caribbean, and Africa, areas where approximately one percent of adults are infected. About one to three percent of infected individuals will eventually develop adult T-cell leukemia after an incubation period, which is usually several decades long. HTLV stimulates T-cell proliferation that could favor mutational events leading to cell transformation.

Acutely transforming retroviruses contain a viral oncogene (v-onc) and induce polyclonal cancers (that is, many different cancer cells are derived in multiple transforming events) at high efficiency within a short time frame (weeks). The v-onc are derived by incorporation and modification (that is, by deletion of introns, mutations, and other such processes) of host-cell oncogenes. The v-onc are often expressed in great quantity, due to the highly active viral LTRs. Most acutely transforming retroviruses are replication-defective, because incorporation of the oncogene deletes an essential gene or genes. They therefore require a helper virus to prop-

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agate. An exception is Rous sarcoma virus, whose genome retains enough of the structural gene sequences to remain capable of replication. see also DNA Libraries; Evolution of Genes; Gene Therapy; HIV; Oncogenes; Overlapping Genes; Reverse Transcriptase; RNA; RNA Polymerases; Virus.

Robert Garry

Bibliography

Varmus, Harold E. "Form and Function of Retroviral Proviruses." Science 216, no. 4548 (1982): 812-820.

Weinberg, Robert A. "How Cancer Arises." Scientific American 275, no. 3 (1996): 62-70.

Reverse Transcriptase

Reverse transcriptase is the replication enzyme of retroviruses. Because it polymerizes DNA precursors, reverse transcriptase is a DNA polymerase. However, whereas cellular DNA polymerases use DNA as a template for making new DNAs, reverse transcriptase uses the single-stranded RNA in retroviruses as the template for synthesizing viral DNA. This unusual process of making DNA from RNA is called "reverse transcription" because it reverses the flow of genetic information (from DNA to RNA, rather than from RNA to DNA found in transcription). Because reverse transcriptase is essential for retroviruses such as HIV-1 (the virus that causes AIDS), it is the target of many antiretroviral therapeutics. Reverse transcriptase is also a molecular tool used in the cloning of genes and the analysis of gene expression.

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