Cell Transformation by RNA Viruses: An Overview

Studies of oncogenic viruses have made seminal contributions to the molecular biology of cancer. Key discoveries include the identification of viral oncogenes and cellular proto-oncogenes, elucidation of signal transduction pathways, and identification of tumor suppressor genes. The origins of cancer virology began almost exactly one hundred years ago with the discovery of avian sarcoma and acute leukemia viruses—RNA-containing viruses of the retrovirus family. The study of animal cancer viruses accelerated beginning in the late 1960s and early 1970s, with the discovery of DNA viruses that could transform cells in culture, and the development of quantitative assays for transformation by DNA and RNA-containing tumor viruses. The discovery of reverse transcriptase in retroviruses in 1970 also greatly accelerated research on these viruses. Indeed RNA and DNA tumor viruses led the way in cancer molecular biology during this era before molecular cloning. It was possible to physically purify virus particles and generate specific hybridization probes for viral DNA and RNA at a time when it was not possible to analyze cellular genes in the same manner. Laboratory studies on RNA and DNA tumor viruses (many of them animal viruses) are highly relevant to human cancer. First, many of the principles of viral oncogenesis elucidated by these studies are directly applicable to human cancers, including those that are not caused by viruses. In addition, a significant percentage of human cancers worldwide (~15%) have a viral involvement. Human DNA tumor viruses include human papillomavirus (HPV, high risk strains), Merkel cell polyomavirus (MPV), the gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV), and hepatitis B virus (HBV). Human RNA viruses that cause cancer include the retrovirus Human T-cell Leukemia virus type I (HTLV-I) and the flavivirus hepatitis C virus (HCV). In addition, AIDS is caused by a retrovirus (HIV-1 and-2); a major complication of the immunodeficiency characteristic of AIDS is the development of cancers. Most of these cancers have an underlying viral involvement (e.g. KSHV and Kaposi's sarcoma, which was first discovered in AIDS patients).