Viruses are intracellular parasites that cannot replicate on their own. They reproduce by infecting host cells and usurping the cellular machinery to produce more virus particles. In their simplest forms, viruses consist only of genomic nucleic acid (either DNA or RNA) surrounded by a protein coat (Figure 1.23). Viruses are important in molecular and cellular biology because they provide simple systems that can be used to investigate the functions of cells. Because virus replication depends on the metabolism of the infected cells, studies of viruses have revealed many fundamental aspects of cell biology.
Figure 1.23 Structure of an animal virus (A) Papillomavirus particles contain a small circular DNA molecule enclosed in a protein coat (the capsid). (B) Electron micrograph of human papillomavirus particles. Artificial color has been added.
The rapid growth and small genome size of viruses have made them especially important for studies of mammalian cells. Most animal viruses replicate and can be readily studied in cultured cells, where they take over the machinery of the cell to produce new virus particles. The genomes of animal viruses are much smaller and simpler than those of cells, ranging from approximately 3000 to 300,000 base pairs and often containing less than a dozen genes. Animal viruses are thus far more manageable than their host cells, making it comparatively easy to follow virus replication and undertake genetic analysis.
Examples in which animal viruses have provided critically important models for investigations of mammalian cells include studies of DNA replication, transcription, RNA processing, and protein transport and secretion.
It is also noteworthy that infection by some animal viruses can convert normal cells into cancer cells (see Molecular Medicine). Studies of such cancer-causing viruses, first described by Peyton Rous in 1911, not only have provided the basis for our current understanding of cancer at the level of cell and molecular biology, but also have led to the elucidation of many of the molecular mechanisms that control animal cell growth and differentiation.
Viruses and Cancer
What Is Cancer?
Cancer is a family of diseases characterized by uncontrolled cell proliferation. The growth of normal animal cells is carefully regulated to meet the needs of the complete organism. In contrast, cancer cells grow in an unregulated manner, ultimately invading and interfering with the function of normal tissues and organs. Cancer is the second most common cause of death (next to heart disease) in the United States. Approximately one out of every three Americans will develop cancer at some point in life and, despite major advances in treatment, nearly one out of every four Americans ultimately die of this disease. Understanding the causes of cancer and developing more effective methods of cancer treatment therefore represent major goals of medical research.
The First Cancer-Causing Virus Cancer is now known to result from mutations in the genes that normally control cell proliferation. The major insights leading to identification of these genes came from studies of viruses that cause cancer in animals, the prototype of which was isolated by Peyton Rous in 1911. Rous found that sarcomas (cancers of connective tissues) in chickens could be transmitted by a virus, now known as Rous sarcoma virus, or RSV. Because RSV has a genome of only 10,000 base pairs, it can be subjected to molecular analysis much more readily than the complex genomes of chickens or other animal cells. Such studies eventually led to identification of a specific cancer-causing gene (onco- gene) carried by the virus, and to the discovery of related genes in normal cells of all vertebrate species, including humans. Some cancers in humans are now known to be caused by viruses; others result from mutations in normal cell genes similar to the oncogene first identified in RSV.
What Viruses Have Taught Us The human cancers that are caused by viruses include cervical and other anogenital cancers (papillomaviruses), liver cancer (hepatitis B and C viruses), and some types of lymphomas (Epstein-Barr virus and human
T-cell lymphotropic virus). Together, these virus-induced cancers account for 15–20% of worldwide cancer incidence. In principle, these cancers could be prevented by vaccination against the responsible viruses, and considerable progress in this area has been made by the development of effective vaccines against hepatitis B virus and human papillomaviruses.
Other human cancers are caused by mutations in normal cell genes, most of which occur during the lifetime of the individual rather than from inheritance. Studies of cancer-causing viruses have led to the identification of many of the genes responsible for non–virus-induced cancers, and to an understanding of the molecular mechanisms responsible for cancer development. Major efforts are now under way to use these insights into the molecular and cellular biology of cancer to develop new approaches to cancer treatment. Indeed, the first designer drug effective in treating a human cancer (the drug imatinib or Gleevec, discussed in Chapter 20) was developed against a gene very similar to the oncogene of RSV.