Oncovirus
Encyclopedia
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 long-standing coevolution between the virus with its host.
Worldwide, the WHO International Agency for Research on Cancer estimated that in 2002 17.8% of human cancers were caused by infection, with 11.9% being caused by one of seven different viruses. The importance of this is that these cancers might be easily prevented through vaccination (e.g., papillomavirus vaccines
), diagnosed with simple blood tests, and treated with less-toxic antiviral compounds.
or mononucleosis for Epstein-Barr virus
. A minority of persons (or animals) will go on to develop cancers after infection. This has complicated determining whether or not a given virus causes cancer. The well-known Koch's Postulates
, are 19th Century constructs developed by Robert Koch
to establish the likelihood for Bacillus anthracis causing anthrax
disease and are not applicable to viral diseases (Firstly, 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 elegantly described the difficulties in using Koch's postulates to virus-induced cancers. Finally, the host restriction for human viruses makes it unethical to experimentally transmit a suspected cancer virus.) Thus, other measures such as A.B. Hill's criteria are more relevant to cancer virology but also face some difficulties 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.
By the early 1950s it was known that viruses could remove and incorporate genes and genetic material in cells. It was suggested that these new genes inserted into cells could make the cell cancerous. Many of these viral oncogenes have been 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 retrovirus
es, 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.
Advances in cancer research have made a vaccines designed to prevent cancer. The hepatitis B vaccine is the first vaccine that has been established to prevent cancer (hepatocellular carcinoma) by preventing infection with the causative virus. In 2006, the U.S. Food and Drug Administration approved a human papilloma virus vaccine, called Gardasil
. The vaccine protects against four HPV types, which together cause 70% of cervical cancers and 90% of genital warts. In March 2007, the US Centers for Disease Control and Prevention
(CDC) Advisory Committee on Immunization Practices
(ACIP) officially recommended that females aged 11–12 receive the vaccine, and indicated that females as young as age 9 and as old as age 26 are also candidates for immunization.
as well as human T-lymphotropic virus
(HTLV-1).
Estimated percent of new cancers attributable to the virus worldwide in 2002. NA indicates not available.
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
that can cause cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. 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 long-standing coevolution between the virus with its host.
Worldwide, the WHO International Agency for Research on Cancer estimated that in 2002 17.8% of human cancers were caused by infection, with 11.9% being caused by one of seven different viruses. The importance of this is that these cancers might be easily prevented through vaccination (e.g., papillomavirus vaccines
HPV vaccine
The human papilloma virus vaccine prevents infection with certain species of human papillomavirus associated with the development of cervical cancer, genital warts, and some less common cancers...
), diagnosed with simple blood tests, and treated with less-toxic antiviral compounds.
Background
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 virusHepatitis B virus
Hepatitis B is an infectious illness caused by hepatitis B virus which infects the liver of hominoidea, including humans, and causes an inflammation called hepatitis. Originally known as "serum hepatitis", the disease has caused epidemics in parts of Asia and Africa, and it is endemic in China...
or mononucleosis for Epstein-Barr virus
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
. A minority of persons (or animals) will go on to develop cancers after infection. This has complicated determining whether or not a given virus causes cancer. The well-known Koch's Postulates
Koch's postulates
Koch's postulates are four criteria designed to establish a causal relationship between a causative microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884 and refined and published by Koch in 1890...
, are 19th Century constructs developed by Robert Koch
Robert Koch
Heinrich Hermann Robert Koch was a German physician. He became famous for isolating Bacillus anthracis , the Tuberculosis bacillus and the Vibrio cholerae and for his development of Koch's postulates....
to establish the likelihood for Bacillus anthracis causing anthrax
Anthrax
Anthrax is an acute disease caused by the bacterium Bacillus anthracis. Most forms of the disease are lethal, and it affects both humans and other animals...
disease and are not applicable to viral diseases (Firstly, 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 elegantly described the difficulties in using Koch's postulates to virus-induced cancers. Finally, the host restriction for human viruses makes it unethical to experimentally transmit a suspected cancer virus.) Thus, other measures such as A.B. Hill's criteria are more relevant to cancer virology but also face some difficulties in determining causality.
Tumor viruses come in a variety of forms: viruses with a DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
, such as adenovirus, and viruses with an RNA genome, like the Hepatitis C virus
Hepatitis C virus
Hepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...
(HCV) can cause cancers, as can retroviruses having both DNA and RNA genomes (Human T-lymphotropic virus
Human T-lymphotropic virus
Human T-cell Lymphotropic Virus Type 1 , also called the Adult T-cell lymphoma virus type 1, a virus that has been seriously implicated in several kinds of diseases including HTLV-I-associated myelopathy, Strongyloides stercoralis hyper-infection, and a virus cancer link for leukemia...
and hepatitis B virus
Hepatitis B virus
Hepatitis B is an infectious illness caused by hepatitis B virus which infects the liver of hominoidea, including humans, and causes an inflammation called hepatitis. Originally known as "serum hepatitis", the disease has caused epidemics in parts of Asia and Africa, and it is endemic in China...
, 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
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
and Kaposi's sarcoma-associated herpesvirus
Kaposi's sarcoma-associated herpesvirus
Kaposi's sarcoma-associated herpesvirus is one of seven currently known human cancer viruses, or oncoviruses. It is also the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. Like other herpesviruses, its informal name is used...
). 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.
Timeline of Discovery
- 1908: Oluf Bang and Vilhelm Ellerman, University of Copenhagen, first demonstrated that avian leukosis virus could be transmitted after cell-free filtration to new chickens, causing leukemia.
- 1910: Peyton Rous at Rockefeller extended Bang and Ellerman's experiments to show filtrable cell-free transmission of a solid tumor sarcoma to chickens. The reasons why chickens are so receptive to such transmission may involve unusual characteristics of stability or instability as they relate to endogenous retroviruses.
- 1933: Richard Edwin ShopeRichard Edwin ShopeRichard Shope was an American virologist who was first to isolate an influenza virus and first to vaccinate animals against influenza. In the 1930s, Shope, a physician at the Rockefeller Institute for Medical Research, identified the causative agent as a virus in the 1918-19 Spanish influenza...
discovered cottontail rabbit papillomavirus or Shope papillomavirus, the first mammalian tumor virus. - 1936: Mouse mammary tumor virusMouse mammary tumor virusMouse mammary tumor virus is a milk transmitted retrovirus like the HTL viruses, HI viruses and BLV. It belongs to the genus betaretroviruses. MMTV was formerly known as Bittner virus, and previously the 'milk factor' referring to the extra-chromosomal vertical transmission of murine breast cancer...
shown by John J. Bittner to be an "extrachromosomal factor" (i.e., virus) transmitted among laboratory strains of mice by breast feeding. This was an extension of work on murine breast cancer caused by a transmissible agent as early as 1915, by A.F. Lathrop and L. Loeb. - 1954: Ludwik GrossLudwik GrossLudwik Gross was a Polish-American virologist who discovered two different tumor viruses, murine leukemia virus and mouse polyomavirus, capable of causing cancers in laboratory mice. Gross was born in Cracow, Poland to a prominent Jewish family and studied for a degree in medicine at the...
, working at the Bronx VA medical center isolated murine polyomavirusPolyomavirusPolyomavirus is the sole genus of viruses within the family Polyomaviridæ. Murine polyomavirus was the first polyomavirus discovered by Ludwik Gross in 1953. Subsequently, many polyomaviruses have been found to infect birds and mammals...
causing a variety of salivary gland and other tumors in specific strains of newborn mice. This was not widely appreciated until the results were confirmed by scientists at NIH reproducing the experiments under the same conditions. - 1961: Simian Vacuolating virus 40 (SV40SV40SV40 is an abbreviation for Simian vacuolating virus 40 or Simian virus 40, a polyomavirus that is found in both monkeys and humans...
) discovered by Eddy at NIH, and Hillman and Sweet at Merck laboratory as a rhesus macaque virus contaminating cells used to make of Salk and Sabin polio vaccines. Several years later it was shown to cause cancer in Syrian hamsters, raising alarm that persists today. Scientific consensus now strongly agrees that this is not likely to cause human cancer although the controversy still persists.
Human Cancer Viruses
- 1964: Anthony EpsteinAnthony EpsteinSir Michael Anthony Epstein CBE, FRS is one of the discoverers of the Epstein-Barr virus.Epstein was educated at St. Paul's School in London, Trinity College, Cambridge and Middlesex Hospital Medical School. Epstein was Professor of Pathology, 1968-85 , and Head of Department, 1968-82 at the...
, Bert AchongBert AchongBert Geoffrey Achong is best known for co-discovering the Epstein-Barr virus through use of electron microscopy. After excelling in school in Trinidad, Achong enrolled at University College Dublin, where he received his medical degree...
and Yvonne Barr identify the first human cancer virus from Burkitt lymphoma cells. A herpesvirus, this virus is formally known as human herpesvirus 4 but more commonly called Epstein-Barr VirusEpstein-Barr virusThe Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
or EBV. Achong, a Trinidadian of Ghanaian ancestry, is frequently forgotten for this work but was central to the electron microscopy that allowed detection. - mid-1960s: Baruch Blumberg first physically isolated and characterized Hepatitis B while at NIH and later Fox Chase Laboratory, receiving the 1976 Nobel Prize in Medicine or Physiology. Although this agent was the clear cause of hepatitis and might contribute to liver cancer hepatocellular carcinomaHepatocellular carcinomaHepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...
, this link was not firmly established until epidemiologic studies were performed in the 1980s by R. Palmer Beasley and others. - 1980: Human T-lymphotropic virus 1 (HTLV I), the first human retrovirus was discovered by Bernard Poiesz and Robert GalloRobert GalloRobert Charles Gallo is an American biomedical researcher. He is best known for his role in the discovery of the Human Immunodeficiency Virus , the infectious agent responsible for the Acquired Immune Deficiency Syndrome , and he has been a major contributor to subsequent HIV research.Gallo is the...
at NIH and Mistuaki Yoshida and coworkers in Japan. - 1984–86: Harald zur HausenHarald zur HausenHarald zur Hausen is a German virologist and professor emeritus. He has done research on cancer of the cervix, where he discovered the role of papilloma viruses, for which he received the Nobel Prize in Physiology or Medicine 2008.-Biography:Zur Hausen was born in Gelsenkirchen, Germany, went to...
, together with Lutz Gissman, discovered first HPV16 and then HPV18 responsible for approximately 70% of cervical cancers. For discovery that human papillomaviruses (HPV) cause human cancer, zur Hausen won a 2008 Nobel Prize. - 1987: Hepatitis C virusHepatitis C virusHepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...
, or HCV, discovered by panning a cDNA library made from diseased tissues for foreign antigens recognized with patient sera. This work was performed by Michael HoughtonMichael HoughtonMichael Alan Houghton was Bishop of Ebbsfleet from 1998 to 1999.Houghton was born on 14 June 1949 and educated at the University of Lancaster. He worked for British Rail and as a teacher before studying for the priesthood. He was a curate at All Hallows' Wellingborough followed by a period...
at ChironChironIn Greek mythology, Chiron was held to be the superlative centaur among his brethren.-History:Like the satyrs, centaurs were notorious for being wild and lusty, overly indulgent drinkers and carousers, given to violence when intoxicated, and generally uncultured delinquents...
, a biotechnology company, and D.W. Bradley at CDCCenters for Disease Control and PreventionThe Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
. Controversy erupted when ChironChironIn Greek mythology, Chiron was held to be the superlative centaur among his brethren.-History:Like the satyrs, centaurs were notorious for being wild and lusty, overly indulgent drinkers and carousers, given to violence when intoxicated, and generally uncultured delinquents...
claimed all rights to the discovery although the work had been performed under contract with the CDC using Bradley's materials and ideas. Eventually, this was amicably settled. HCV was subsequently shown to be a major contributor to liver cancer (hepatocellular carcinoma) worldwide. - 1994: Patrick S. MoorePatrick S. MoorePatrick S. Moore is an American virologist and epidemiologist who co-discovered together with his wife, Yuan Chang, two different human viruses causing the AIDS-related cancer Kaposi's sarcoma and the skin cancer Merkel cell carcinoma...
and Yuan ChangYuan ChangYuan Chang is an American virologist and pathologist who co-discovered Kaposi's sarcoma-associated herpesvirus and Merkel cell polyomavirus, two of the seven known human cancer viruses....
(a husband and wife team then at Columbia UniversityColumbia UniversityColumbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
) working together with Frank Lee and Ethel Cesarman isolated Kaposi sarcoma-associated herpesvirus (KSHV or HHV8) using representational difference analysisRepresentational Difference AnalysisRepresentational Difference Analysis is a technique used in biological research to find sequence differences in two genomic or cDNA samples. Genomes or cDNA sequences from two samples are PCR amplified and differences analyzed using subtractive DNA hybridization...
. This search was prompted from work by V. Beral, T. Peterman and H. Jaffe who showed from accumulating evidence from the epidemic of Kaposi sarcoma associated with AIDS, that this cancer must have another infectious cause besides HIV itself. This agent was predicted to be a new virus. Subsequent studies revealed that KSHV is indeed the "KS agent" and is responsible for the epidemiologic patterns of KS and related cancers. - 2008: Chang and Moore, now at the University of Pittsburgh Cancer InstituteUniversity of Pittsburgh Cancer InstituteThe University of Pittsburgh Cancer Institute is a National Cancer Institute -designated Comprehensive Cancer Center located in the Hillman Cancer Center in the Shadyside neighborhood of Pittsburgh, Pennsylvania, United States...
, developed a new method to identify cancer viruses based on computer subtraction of human sequences from a tumor transcriptomeTranscriptomeThe transcriptome is the set of all RNA molecules, including mRNA, rRNA, tRNA, and other non-coding RNA produced in one or a population of cells.-Scope:...
, called digital transcriptome subtraction (DTS). DTS was used to isolate DNA fragments of Merkel cell polyomavirusMerkel cell polyomavirusMerkel cell polyomavirus was first described in January 2008. MCV is one of seven known human tumor viruses. It is suspected to cause the majority of cases of Merkel cell carcinoma, a rare but aggressive form of skin cancer. Approximately 80% of Merkel cell carcinoma tumors have been found to be...
from a Merkel cell carcinoma and it is now believed that this virus causes 70–80% of these cancers. This is the first polyomavirus to be well-established as the cause for a human cancer.
History
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.By the early 1950s it was known that viruses could remove and incorporate genes and genetic material in cells. It was suggested that these new genes inserted into cells could make the cell cancerous. Many of these viral oncogenes have been discovered and identified to cause cancer.
The main viruses associated with human cancers are human papillomavirus
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
, hepatitis B and hepatitis C virus, Epstein-Barr virus
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
, human T-lymphotropic virus
Human T-lymphotropic virus
Human T-cell Lymphotropic Virus Type 1 , also called the Adult T-cell lymphoma virus type 1, a virus that has been seriously implicated in several kinds of diseases including HTLV-I-associated myelopathy, Strongyloides stercoralis hyper-infection, and a virus cancer link for leukemia...
, Kaposi's sarcoma-associated herpesvirus (KSHV
Kaposi's sarcoma-associated herpesvirus
Kaposi's sarcoma-associated herpesvirus is one of seven currently known human cancer viruses, or oncoviruses. It is also the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. Like other herpesviruses, its informal name is used...
) and Merkel cell polyomavirus
Merkel cell polyomavirus
Merkel cell polyomavirus was first described in January 2008. MCV is one of seven known human tumor viruses. It is suspected to cause the majority of cases of Merkel cell carcinoma, a rare but aggressive form of skin cancer. Approximately 80% of Merkel cell carcinoma tumors have been found to be...
. 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 retrovirus
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
es, 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
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
, can induce a chronic viral infection that leads to liver cancer
Hepatocellular carcinoma
Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...
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
Viral hepatitis
Viral hepatitis is liver inflammation due to a viral infection. It may present in acute or chronic forms. The most common causes of viral hepatitis are the five unrelated hepatotropic viruses Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis D, and Hepatitis E...
transmission and disease.
Advances in cancer research have made a vaccines designed to prevent cancer. The hepatitis B vaccine is the first vaccine that has been established to prevent cancer (hepatocellular carcinoma) by preventing infection with the causative virus. In 2006, the U.S. Food and Drug Administration approved a human papilloma virus vaccine, called Gardasil
Gardasil
Gardasil , also known as Gardisil or Silgard, is a vaccine for use in the prevention of certain types of human papillomavirus , specifically HPV types 6, 11, 16 and 18. HPV types 16 and 18 cause an estimated 70% of cervical cancers, and are responsible for most HPV-induced anal, vulvar, vaginal,...
. The vaccine protects against four HPV types, which together cause 70% of cervical cancers and 90% of genital warts. In March 2007, the US Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
(CDC) Advisory Committee on Immunization Practices
Advisory Committee on Immunization Practices
The Advisory Committee on Immunization Practices provides advice and guidance on effective control of vaccine-preventable diseases in the U.S. civilian population. The ACIP develops written recommendations for routine administration of vaccines to the pediatric and adult populations, along with...
(ACIP) officially recommended that females aged 11–12 receive the vaccine, and indicated that females as young as age 9 and as old as age 26 are also candidates for immunization.
Brief history
In the 1960s, the replication process of RNA virus was believed to be similar to other single-stranded RNA. Single-stranded RNA replication involves RNA-dependent RNA synthesis which meant that virus-coding enzymes would make partial double-stranded RNA. This belief was proven to be incorrect because there were no double-stranded RNA found in the retrovirus cell. In the 1964, Howard Temin proposed a provirus hypothesis, but shortly after reverse transcription in the retrovirus genome was discovered.Description of virus
All retroviruses have three major coding domains; gag, pol and env. In the gag region of the virus, the synthesis of the internal virion proteins are maintained which make up the matrix, capsid and nucleocapsid proteins. In pol, the information for the reverse transcription and integration enzymes are stored. In env, it is derived from the surface and transmembrane for the viral envelope protein. There is a fourth coding domain which is smaller, but exists in all retroviruses. Pol is the domain that encodes the virion protease.Retrovirus enters host cell
The retrovirus begins the journey into a host cell by attaching a surface glycoprotein to the cell's plasma membrane receptor. Once inside the cell, the retrovirus goes through reverse transcription in the cytoplasm and generates a double-stranded DNA copy of the RNA genome. Reverse transcription also produces identical structures known as long terminal repeats (LTRs). Long terminal repeats are at the ends of the DNA strands and regulates viral gene expression. The viral DNA is then translocated into the nucleus where one strand of the retroviral genome is put into the chromosomal DNA by the help of the virion intergrase. At this point the retrovirus is referred to as provirus. Once in the chromosomal DNA, the provirus is transcribed by the cellular RNA polymerase II. The transcription leads to the splicing and full-length mRNAs and full-length progeny virion RNA. The virion protein and progeny RNA assemble in the cytoplasm and leave the cell, whereas the other copies send translated viral messages in the cytoplasmDNA viruses
- Human papilloma virus (HPV), a DNA virus, causes transformationMalignant transformationMalignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as malignant degeneration of a previously existing benign tumor....
in cells through interfering with tumor suppressor proteins such as p53P53p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
. Interfering with the action of p53 allows a cell infected with the virus to move into a different stage of the cell cycle, enabling the virus genome to be replicated. Forcing the cell into the S phase of the cell cycleCell cycleThe cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
could cause the cell to become transformed. Some types of HPV increase the risk of, e.g., cervical cancerCervical cancerCervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
. - Kaposi's sarcoma-associated herpesvirusKaposi's sarcoma-associated herpesvirusKaposi's sarcoma-associated herpesvirus is one of seven currently known human cancer viruses, or oncoviruses. It is also the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. Like other herpesviruses, its informal name is used...
(KSHV or HHV-8) is associated with Kaposi’s sarcoma, a type of skin cancer. - Epstein-Barr virusEpstein-Barr virusThe Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
(EBV or HHV-4) is associated with four types of cancers - Merkel cell polyomavirusMerkel cell polyomavirusMerkel cell polyomavirus was first described in January 2008. MCV is one of seven known human tumor viruses. It is suspected to cause the majority of cases of Merkel cell carcinoma, a rare but aggressive form of skin cancer. Approximately 80% of Merkel cell carcinoma tumors have been found to be...
a polyoma virus is associated with the development of Merkel cell carcinomaMerkel cell carcinomaMerkel cell carcinoma Merkel cell carcinoma Merkel cell carcinoma (also known as a "Cutaneous apudoma," "Primary neuroendocrine carcinoma of the skin," "Primary small cell carcinoma of the skin," and "Trabecular carcinoma of the skin"... - Human cytomegalovirus (CMV or HHV-5) is associated with mucoepidermoid carcinomaMucoepidermoid carcinomaMucoepidermoid carcinoma is the most common type of salivary gland malignancy in children. Mucoepidermoid carcinoma can also be found in other organs, as bronchi, lacrimal sac and thyroid.Mucicarmine staining is one stain used by pathologist for detection....
and possibly other malignancies.
RNA viruses
Not all oncoviruses are DNA viruses. Some RNA viruses have also been associated such as the hepatitis C virusHepatitis C virus
Hepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...
as well as human T-lymphotropic virus
Human T-lymphotropic virus
Human T-cell Lymphotropic Virus Type 1 , also called the Adult T-cell lymphoma virus type 1, a virus that has been seriously implicated in several kinds of diseases including HTLV-I-associated myelopathy, Strongyloides stercoralis hyper-infection, and a virus cancer link for leukemia...
(HTLV-1).
Overview table
| Virus | Percent of cancers | Associated cancer types |
|---|---|---|
| Hepatitis viruses, including hepatitis B (HBV) and hepatitis C Hepatitis C Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years... (HCV) |
4.9 | Hepatocellular carcinoma Hepatocellular carcinoma Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States... (liver cancer Liver cancer Liver tumors or hepatic tumors are tumors or growths on or in the liver . Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. These growths can be benign or malignant... ). |
| Human T-lymphotropic virus Human T-lymphotropic virus Human T-cell Lymphotropic Virus Type 1 , also called the Adult T-cell lymphoma virus type 1, a virus that has been seriously implicated in several kinds of diseases including HTLV-I-associated myelopathy, Strongyloides stercoralis hyper-infection, and a virus cancer link for leukemia... (HTLV) |
0.03 | Tropical spastic paraparesis Tropical spastic paraparesis Tropical spastic paraparesis , also known as HTLV-associated myelopathy or chronic progressive myelopathy, is an infection of the spinal cord by Human T-lymphotropic virus resulting in paraparesis, weakness of the legs... and adult T-cell leukemia Adult T-cell leukemia Adult T-cell leukemia/lymphoma is a rare cancer of the immune system's own T-cells.Human T cell leukemia/lymphotropic virus type 1 is believed to be the cause of it, in addition to several other diseases.-Signs and symptoms:... |
| Human papillomaviruses (HPV) | 5.2 | Cancers of cervix Cervical cancer Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages... , anus Anal cancer Anal cancer is a type of cancer which arises from the anus, the distal orifice of the gastrointestinal tract. It is a distinct entity from the more common colorectal cancer. The etiology, risk factors, clinical progression, staging, and treatment are all different. Anal cancer is typically a... , penis Carcinoma of the penis Penile cancer is a malignant growth found on the skin or in the tissues of the penis. A Squamous cell carcinoma usually originating in the glans or foreskin is by far the most common type, occurring in 9 out of 10 cases. Penis cancer tends to develop in men over the age of sixty. Penile cancer is... , vulva/vagina Vulvar cancer Vulvar cancer, a malignant invasive growth in the vulva, accounts for about 4 % of all gynecological cancers and typically affects women in later life. It is estimated that in the United States in 2006 about 3,740 new cases will be diagnosed and about 880 women will die as a result of vulvar cancer... , and some cancers of the head and neck HPV-positive oropharyngeal cancer Human papillomavirus -positive oropharyngeal cancer also known as HPV16+ oropharyngeal cancer or HPV+ OPC is a recognized subtype of Oropharyngeal squamous cell carcinomas , associated with the HPV type 16 virus.-Causes:... . |
| Kaposi’s sarcoma-associated herpesvirus | 0.9 | Kaposi’s sarcoma, multicentric Castleman's disease and primary effusion lymphoma Primary effusion lymphoma -Causes:It is caused by Kaposi's sarcoma-associated herpesvirus , also known as human herpesvirus 8 .In most cases, the lymphoma cells are also infected with Epstein Barr virus .... |
| Merkel cell polyomavirus Merkel cell polyomavirus Merkel cell polyomavirus was first described in January 2008. MCV is one of seven known human tumor viruses. It is suspected to cause the majority of cases of Merkel cell carcinoma, a rare but aggressive form of skin cancer. Approximately 80% of Merkel cell carcinoma tumors have been found to be... |
NA | Merkel cell carcinoma Merkel cell carcinoma Merkel cell carcinoma Merkel cell carcinoma Merkel cell carcinoma (also known as a "Cutaneous apudoma," "Primary neuroendocrine carcinoma of the skin," "Primary small cell carcinoma of the skin," and "Trabecular carcinoma of the skin"... |
| Epstein–Barr virus (EBV) | NA | Burkitt’s lymphoma, Hodgkin’s lymphoma, post-transplantation lymphoproliferative disease and Nasopharyngeal carcinoma Nasopharyngeal carcinoma Nasopharyngeal carcinoma is the most common cancer originating in the nasopharynx, the uppermost region of the pharynx , behind the nose where the nasal passages and auditory tubes join the remainder of the upper respiratory tract. NPC differs significantly from other cancers of the head and neck... . |
Estimated percent of new cancers attributable to the virus worldwide in 2002. NA indicates not available.
See also
- CarcinogenCarcinogenA carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
- Oncogenic
- OncogeneOncogeneAn oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...
- Adult T-cell leukemia/lymphoma
- Cancer bacteriaCancer bacteriaCancer bacteria are bacterial infectious organisms that are known or suspected to cause cancer. While cancer-associated bacteria have long been considered to be opportunistic , there is some evidence that bacteria may be directly carcinogenic. The strongest evidence to date involves the bacterium H...
- Oncolytic virusOncolytic virusAn oncolytic virus is a virus that preferentially infects and lyses cancer cells; these have obvious functions for cancer therapy, both by direct destruction of the tumour cells, and, if modified, as vectors enabling genes expressing anticancer proteins to be delivered specifically to the tumor...
, a virus that infects and kills cancer cells