Oncovirus

An oncovirus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin.It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with 'tumor virus' or 'cancer virus'. The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein. An oncovirus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin.It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with 'tumor virus' or 'cancer virus'. The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein. The World Health Organization's International Agency for Research on Cancer estimated that in 2002, infection caused 17.8% of human cancers, with 11.9% caused by one of seven viruses. These cancers might be easily prevented through vaccination (e.g., papillomavirus vaccines), diagnosed with simple blood tests, and treated with less-toxic antiviral compounds. Generally, tumor viruses cause little or no disease after infection in their hosts, or cause non-neoplastic diseases such as acute hepatitis for hepatitis B virus or mononucleosis for Epstein–Barr virus. A minority of persons (or animals) will go on to develop cancers after infection. This has complicated efforts to determine whether or not a given virus causes cancer. The well-known Koch's postulates, 19th-century constructs developed by Robert Koch to establish the likelihood that Bacillus anthracis will cause anthrax disease, are not applicable to viral diseases. (Firstly, this is because viruses cannot truly be isolated in pure culture—even stringent isolation techniques cannot exclude undetected contaminating viruses with similar density characteristics, and viruses must be grown on cells. Secondly, asymptomatic virus infection and carriage is the norm for most tumor viruses, which violates Koch's third principle. Relman and Fredericks have described the difficulties in applying Koch's postulates to virus-induced cancers. Finally, the host restriction for human viruses makes it unethical to experimentally transmit a suspected cancer virus.) Other measures, such as A. B. Hill's criteria, are more relevant to cancer virology but also have some limitations in determining causality. Tumor viruses come in a variety of forms: Viruses with a DNA genome, such as adenovirus, and viruses with an RNA genome, like the Hepatitis C virus (HCV), can cause cancers, as can retroviruses having both DNA and RNA genomes (Human T-lymphotropic virus and hepatitis B virus, which normally replicates as a mixed double and single-stranded DNA virus but also has a retroviral replication component). In many cases, tumor viruses do not cause cancer in their native hosts but only in dead-end species. For example, adenoviruses do not cause cancer in humans but are instead responsible for colds, conjunctivitis and other acute illnesses. They only become tumorigenic when infected into certain rodent species, such as Syrian hamsters. Some viruses are tumorigenic when they infect a cell and persist as circular episomes or plasmids, replicating separately from host cell DNA (Epstein–Barr virus and Kaposi's sarcoma-associated herpesvirus). Other viruses are only carcinogenic when they integrate into the host cell genome as part of a biological accident, such as polyomaviruses and papillomaviruses. A direct oncogenic viral mechanism involves either insertion of additional viral oncogenic genes into the host cell or to enhance already existing oncogenic genes (proto-oncogenes) in the genome. Indirect viral oncogenicity involves chronic nonspecific inflammation occurring over decades of infection, as is the case for HCV-induced liver cancer. These two mechanisms differ in their biology and epidemiology: direct tumor viruses must have at least one virus copy in every tumor cell expressing at least one protein or RNA that is causing the cell to become cancerous. Because foreign virus antigens are expressed in these tumors, persons who are immunosuppressed such as AIDS or transplant patients are at higher risk for these types of cancers. Chronic indirect tumor viruses, on the other hand, can be lost (at least theoretically) from a mature tumor that has accumulated sufficient mutations and growth conditions (hyperplasia) from the chronic inflammation of viral infection. In this latter case, it is controversial but at least theoretically possible that an indirect tumor virus could undergo 'hit-and-run' and so the virus would be lost from the clinically diagnosed tumor. In practical terms, this is an uncommon occurrence if it does occur. The theory that cancer could be caused by a virus began with the experiments of Oluf Bang and Vilhelm Ellerman in 1908 who first show that avian erythroblastosis (a form of chicken leukemia) could be transmitted by cell-free extracts. This was subsequently confirmed for solid tumors in chickens in 1910-1911 by Peyton Rous, and for liquid cancer in mice by Charlotte Friend. By the early 1950s, it was known that viruses could remove and incorporate genes and genetic material in cells. It was suggested that such types of viruses could cause cancer by introducing new genes into the genome. Genetic analysis of mice infected with Friend virus confirmed that retroviral integration could disrupt tumor suppressor genes, causing cancer. Subsequently, many viral oncogenes were subsequently discovered and identified to cause cancer. The main viruses associated with human cancers are human papillomavirus, hepatitis B and hepatitis C virus, Epstein–Barr virus, human T-lymphotropic virus, Kaposi's sarcoma-associated herpesvirus (KSHV) and Merkel cell polyomavirus. Experimental and epidemiological data imply a causative role for viruses and they appear to be the second most important risk factor for cancer development in humans, exceeded only by tobacco usage. The mode of virally induced tumors can be divided into two, acutely transforming or slowly transforming. In acutely transforming viruses, the viral particles carry a gene that encodes for an overactive oncogene called viral-oncogene (v-onc), and the infected cell is transformed as soon as v-onc is expressed. In contrast, in slowly transforming viruses, the virus genome is inserted, especially as viral genome insertion is an obligatory part of retroviruses, near a proto-oncogene in the host genome. The viral promoter or other transcription regulation elements in turn cause overexpression of that proto-oncogene, which in turn induces uncontrolled cellular proliferation. Because viral genome insertion is not specific to proto-oncogenes and the chance of insertion near that proto-oncogene is low, slowly transforming viruses have very long tumor latency compared to acutely transforming viruses, which already carry the viral oncogene. Hepatitis viruses, including hepatitis B and hepatitis C, can induce a chronic viral infection that leads to liver cancer in 0.47% of hepatitis B patients per year (especially in Asia, less so in North America), and in 1.4% of hepatitis C carriers per year. Liver cirrhosis, whether from chronic viral hepatitis infection or alcoholism, is associated with the development of liver cancer, and the combination of cirrhosis and viral hepatitis presents the highest risk of liver cancer development. Worldwide, liver cancer is one of the most common, and most deadly, cancers due to a huge burden of viral hepatitis transmission and disease.