RNA-Dependent Synthesis of RNA and DNA:- Some Retroviruses Cause Cancer and AIDS
Retroviruses have featured prominently in recent advances in the molecular understanding of cancer. Most retroviruses do not kill their host cells but remain integrated in the cellular DNA, replicating when the cell di vides. Some retroviruses, classified as RNA tumor viruses, contain an oncogene that can cause the cell to grow abnormally . The first retrovirus of this type to be studied was the Rous sarcoma virus (also called avian sarcoma virus; Fig.1), named for F. Peyton Rous, who studied chicken tumors now known to be caused by this virus. Since the initial discovery of oncogenes by Harold Varmus and Michael Bishop, many dozens of such genes have been found in retroviruses. The human immunodeficiency virus (HIV), which causes acquired immune deficiency syndrome (AIDS), is a retrovirus. Identified in 1983, HIV has an RNA genome with standard retroviral genes along with several other unusual genes (Fig. 2). Unlike many other retroviruses, HIV kills many of the cells it infects (principally T lymphocytes) rather than causing tumor formation. This gradually leads to suppression of the immune system in the host organism. The reverse transcriptase of HIV is even more error prone than other known reverse transcriptases—ten times more so— resulting in high mutation rates in this virus. One or more errors are generally made every time the viral genome is replicated, so any two viral RNA molecules are likely to differ. Many modern vaccines for viral infections consist of one or more coat proteins of the virus, produced by methods described in Chapter 9. These proteins are not infectious on their own but stimulate the immune system to recognize and resist subsequent viral invasions . Because of the high error rate of the HIV reverse transcriptase, the env gene in this virus (along with the rest of the genome) undergoes very rapid mutation, complicating the development of an effective vaccine. However, repeated cycles of cell invasion and replication are needed to propagate an HIV infection, so inhibition of viral enzymes offers promise as an effective therapy. The HIV protease is targeted by a class of drugs called protease inhibitors. Re verse transcriptase is the target of some additional drugs widely used to treat HIV-infected individuals (Box 26–2).
FIGURE 1 Rous sarcoma virus genome. The src gene encodes a tyrosine-specific protein kinase, one of a class of enzymes known to function in systems that affect cell division, cell-cell interactions, and intercellular communication (Chapter 12). The same gene is found in chicken DNA (the usual host for this virus) and in the genomes of many other eukaryotes, including humans. When associated with the Rous sarcoma virus, this oncogene is often expressed at abnormally high levels, contributing to unregulated cell division and cancer.
FIGURE 2 The genome of HIV, the virus that causes AIDS. In addition to the typical retroviral genes, HIV contains several small genes with a variety of functions (not identified here, and not all known). Some of these genes overlap . Alternative splicing mechanisms produce many different proteins from this small (9.7x103 nucleotides) genome .
