retrovirus A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase ...

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and evidenc ...

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

retinoblastoma protein The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated ''Rb'', ''RB'' or ''RB1'') is a proto-oncogenic tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive ...

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...

International Agency for Research on Cancer The International Agency for Research on Cancer (IARC; french: Centre International de Recherche sur le Cancer, CIRC) is an intergovernmental agency forming part of the World Health Organization of the United Nations. Its role is to conduct and ...

neoplastic A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

hepatitis B virus ''Hepatitis B virus'' (HBV) is a partially double-stranded DNA virus, a species of the genus ''Orthohepadnavirus'' and a member of the ''Hepadnaviridae'' family of viruses. This virus causes the disease hepatitis B. Disease Despite there bein ...

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...

Koch's postulates Koch's postulates ( )"Koch"
''

Robert Koch Heinrich Hermann Robert Koch ( , ; 11 December 1843 – 27 May 1910) was a German physician and microbiologist. As the discoverer of the specific causative agents of deadly infectious diseases including tuberculosis, cholera (though the Vibrio ...

to establish the likelihood that ''

Bacillus anthracis ''Bacillus anthracis'' is a gram-positive and rod-shaped bacterium that causes anthrax, a deadly disease to livestock and, occasionally, to humans. It is the only permanent ( obligate) pathogen within the genus ''Bacillus''. Its infection is a ...

'' will cause

anthrax Anthrax is an infection caused by the bacterium ''Bacillus anthracis''. It can occur in four forms: skin, lungs, intestinal, and injection. Symptom onset occurs between one day and more than two months after the infection is contracted. The sk ...

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. Viral Tegument

Tumor viruses come in a variety of forms: Viruses with a DNA

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

, such as

adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from the ...

, and viruses with an RNA genome, like the

hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepato ...

(HCV), can cause cancers, as can retroviruses having both DNA and RNA genomes (

Human T-lymphotropic virus The human T-lymphotropic virus, human T-cell lymphotropic virus, or human T-cell leukemia-lymphoma virus (HTLV) family of viruses are a group of human retroviruses that are known to cause a type of cancer called adult T-cell leukemia/lymphoma and ...

and

hepatitis B virus ''Hepatitis B virus'' (HBV) is a partially double-stranded DNA virus, a species of the genus ''Orthohepadnavirus'' and a member of the ''Hepadnaviridae'' family of viruses. This virus causes the disease hepatitis B. Disease Despite there bein ...

, 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

episome An episome is a special type of plasmid, which remains as a part of the eukaryotic genome without integration. Episomes manage this by replicating together with the rest of the genome and subsequently associating with metaphase chromosomes during m ...

s or plasmids, replicating separately from host cell DNA (

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...

and

Kaposi's sarcoma-associated herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is ''Human gammaherpesvirus 8'', or HHV-8 in short. Like other 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.

Oncogenic viral mechanism

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 An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

) in the genome. For example, it has been shown that vFLIP and vCyclin interfere with the TGF-β signaling pathway indirectly by inducing oncogenic host mir17-92 cluster. 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

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s 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.

DNA oncoviruses

Anaplastic astrocytoma - p53 - very high mag

DNA oncoviruses typically impair two families of tumor suppressor proteins: tumor proteins

p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

and the

retinoblastoma protein The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated ''Rb'', ''RB'' or ''RB1'') is a proto-oncogenic tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive ...

s (Rb). It is evolutionarily advantageous for viruses to inactivate p53 because p53 can trigger cell cycle arrest or apoptosis in infected cells when the virus attempts to replicate its DNA. Similarly, Rb proteins regulate many essential cell functions, including but not limited to a crucial cell cycle checkpoint, making them a target for viruses attempting to interrupt regular cell function. While several DNA oncoviruses have been discovered, three have been studied extensively.

Adenoviruses Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from thei ...

can lead to tumors in rodent models but do not cause cancer in humans; however, they have been exploited as delivery vehicles in gene therapy for diseases such as cystic fibrosis and cancer.

Simian virus 40 SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses, SV40 is a DNA virus that has the potential to cause tumors in animals, but most often ...

(SV40), a

polyomavirus ''Polyomaviridae'' is a family of viruses whose natural hosts are primarily mammals and birds. As of 2020, there are six recognized genera and 117 species, five of which are unassigned to a genus. 14 species are known to infect humans, while othe ...

, can cause tumors in rodent models but is not oncogenic in humans. This phenomenon has been one of the major controversies of oncogenesis in the 20th century because an estimated 100 million people were inadvertently exposed to SV40 through polio vaccines. The

human papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...

-16 (HPV-16) has been shown to lead to cervical cancer and other cancers, including head and neck cancer. These three viruses have parallel mechanisms of action, forming an archetype for DNA oncoviruses. All three of these DNA oncoviruses are able to integrate their DNA into the host cell, and use this to transcribe it and transform cells by bypassing the G1/S checkpoint of the cell cycle.

Integration of viral DNA

DNA oncoviruses transform infected cells by integrating their DNA into the host cell's genome. The DNA is believed to be inserted during transcription or replication, when the two annealed strands are separated. This event is relatively rare and generally unpredictable; there seems to be no deterministic predictor of the site of integration. After integration, the host's cell cycle loses regulation from Rb and p53, and the cell begins cloning to form a tumor.

G1/S Checkpoint

Rb and p53 regulate the transition between G1 and

S phase S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during ...

, arresting the cell cycle before DNA replication until the appropriate checkpoint inputs, such as DNA damage repair, are completed. p53 regulates the p21 gene, which produces a protein which binds to the Cyclin D-Cdk4/6 complex. This prevents Rb phosphorylation and prevents the cell from entering S phase. In mammals, when Rb is active (unphosphorylated), it inhibits the

E2F E2F is a group of genes that encodes a family of transcription factors (TF) in higher eukaryotes. Three of them are activators: E2F1, 2 and E2F3a. Six others act as suppressors: E2F3b, E2F4-8. All of them are involved in the cell cycle regulation a ...

family of transcription factors, which regulate the

Cyclin E Cyclin E is a member of the cyclin family. Cyclin E binds to G1 phase Cdk2, which is required for the transition from G1 to S phase of the cell cycle that determines initiation of DNA duplication. The Cyclin E/CDK2 complex phosphorylates p27 ...

-

Cdk2 Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the ''CDK2'' gene. The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein ...

complex, which inhibits Rb, forming a positive feedback loop, keeping the cell in G1 until the input crosses a threshold. To drive the cell into S phase prematurely, the viruses must inactivate p53, which plays a central role in the G1/S checkpoint, as well as Rb, which, though downstream of it, is typically kept active by a positive feedback loop.

Inactivation of p53

Viruses employ various methods of inactivating p53. The

adenovirus E1B protein Adenovirus E1B protein usually refers to one of two proteins transcribed from the E1B gene of the adenovirus: a 55kDa protein and a 19kDa protein. These two proteins are needed to block apoptosis in adenovirus-infected cells. E1B proteins work to p ...

(55K) prevents p53 from regulating genes by binding to the site on p53 which binds to the genome. In SV40, the

large T antigen The large tumor antigen (also called the large T-antigen and abbreviated LTag or LT) is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. LTag is expressed early in the infectious cycle and is essent ...

(LT) is an analogue; LT also binds to several other cellular proteins, such as

p107 The P107 was a World War II French half-track. History In the 1920s and 1930s Citroën developed a long line of half-tracks based on the Kégresse patent. In 1934, the company introduced its newest and more powerful P107 model as a successor t ...

and p130, on the same residues. LT binds to p53's binding domain on the DNA (rather than on the protein), again preventing p53 from appropriately regulating genes. HPV instead degrades p53: the HPV protein E6 binds to a cellular protein called the E6-associated protein (E6-AP, also known as

UBE3A Ubiquitin-protein ligase E3A (UBE3A) also known as E6AP ubiquitin-protein ligase (E6AP) is an enzyme that in humans is encoded by the ''UBE3A'' gene. This enzyme is involved in targeting proteins for degradation within cells. Protein degradation ...

), forming a complex which causes the rapid and specific

ubiquitination Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...

of p53.

Inactivation of Rb

Rb is inactivated (thereby allowing the G1/S transition to progress unimpeded) by different but analogous viral oncoproteins. The

adenovirus early region 1A Adenovirus early region 1A (''E1A'') is a gene expressed during adenovirus replication to produce a variety of E1A proteins. It is expressed during the early phase of the viral life span. ''E1A'' encodes two major proteins in Ad5, translated after ...

(E1A) is an oncoprotein which binds to Rb and can stimulate transcription and transform cells. SV40 uses the same protein for inactivating Rb, LT, to inactivate p53. HPV contains a protein, E7, which can bind to Rb in much the same way. Rb can be inactivated by phosphorylation, or by being bound to a viral oncoprotein, or by mutations—mutations which prevent oncoprotein binding are also associated with cancer.

Variations

DNA oncoviruses typically cause cancer by inactivating p53 and Rb, thereby allowing unregulated cell division and creating tumors. There may be many different mechanisms which have evolved separately; in addition to those described above, for example, the

Human Papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...

inactivates p53 by sequestering it in the cytoplasm. SV40 has been well studied and does not cause cancer in humans, but a recently discovered analogue called

Merkel cell polyomavirus Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called d ...

has been associated with

Merkel cell carcinoma Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer occurring in about 3 people per 1,000,000 members of the population. It is also known as cutaneous APUDoma, Primary tumor, primary neuroendocrine tumor, neuroendocrine carcinoma of ...

, a form of skin cancer. The Rb binding feature is believed to be the same between the two viruses.

RNA oncoviruses

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 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 A gag is usually an item or device designed to prevent speech, often as a restraint device to stop the subject from calling for help and keep its wearer silent. This is usually done by blocking the mouth, partially or completely, or attempting ...

'', ''pol'' and ''

env env is a shell command for Unix and Unix-like operating systems. It is used to either print a list of environment variables or run another utility in an altered environment without having to modify the currently existing environment. Using 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 cytoplasm.

Classification

DNA viruses

*

Human papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...

(HPV), a DNA virus, causes

transformation Transformation may refer to: Science and mathematics In biology and medicine * Metamorphosis, the biological process of changing physical form after birth or hatching * Malignant transformation, the process of cells becoming cancerous * Trans ...

in cells through interfering with tumor suppressor proteins such as

p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

. 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 cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

could cause the cell to become transformed. Human papillomavirus infection is a major cause of

cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...

,

vulvar cancer Vulvar cancer is a cancer of the vulva, the outer portion of the female genitals. It most commonly affects the labia majora. Less often, the labia minora, clitoris, or vaginal glands are affected. Symptoms include a lump, itchiness, changes in t ...

,

vaginal cancer Vaginal cancer is an extraordinarily rare form of cancer that develops in the tissue of the vagina. Primary vaginal cancer originates from the vaginal tissue – most frequently squamous cell carcinoma, but primary vaginal adenocarcinoma, sarcoma ...

,

penis cancer Penile cancer is cancer that develops in the skin or tissues of the penis. Symptoms may include abnormal growth, an ulcer or sore on the skin of the penis, and bleeding or foul smelling discharge. Risk factors include phimosis (inability to retrac ...

,

anal cancer Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. Symptoms may include bleeding from the anus or a lump near the anus. Other symptoms may include pain, itchiness, or discharge from the anus. ...

, and HPV-positive

oropharyngeal cancer Oropharyngeal cancer (OPC), also known as oropharyngeal squamous cell carcinoma (OPSCC) and tonsil cancer, is a disease in which abnormal cells with the potential to both grow locally and spread to other parts of the body are found in the oral ca ...

s. There are nearly 200 distinct human papillomaviruses (HPVs), and many HPV types are carcinogenic. *

Hepatitis B virus ''Hepatitis B virus'' (HBV) is a partially double-stranded DNA virus, a species of the genus ''Orthohepadnavirus'' and a member of the ''Hepadnaviridae'' family of viruses. This virus causes the disease hepatitis B. Disease Despite there bein ...

(HBV) is associated with Hepatocarcinoma *

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...

(EBV or HHV-4) is associated with four types of cancers *

Human cytomegalovirus ''Human betaherpesvirus 5'', also called human cytomegalovirus (HCMV), is species of virus in the genus ''Cytomegalovirus'', which in turn is a member of the viral family known as ''Herpesviridae'' or herpesviruses. It is also commonly called ...

(CMV or HHV-5) is associated with

mucoepidermoid carcinoma Mucoepidermoid carcinoma (MEC) is the most common type of minor salivary gland malignancy in adults. Mucoepidermoid carcinoma can also be found in other organs, such as bronchi, lacrimal sac, and thyroid gland. Mucicarmine staining is one stain us ...

and possibly other malignancies. *

Kaposi's sarcoma-associated herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is ''Human gammaherpesvirus 8'', or HHV-8 in short. Like other herpesvirus ...

(KSHV or HHV-8) is associated with

Kaposi's sarcoma Kaposi's sarcoma (KS) is a type of cancer that can form masses in the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limite ...

, a type of skin cancer. *

Merkel cell polyomavirus Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called d ...

a

polyoma virus ''Polyomaviridae'' is a family of viruses whose natural hosts are primarily mammals and birds. As of 2020, there are six recognized genera and 117 species, five of which are unassigned to a genus. 14 species are known to infect humans, while othe ...

is associated with the development of

Merkel cell carcinoma Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer occurring in about 3 people per 1,000,000 members of the population. It is also known as cutaneous APUDoma, Primary tumor, primary neuroendocrine tumor, neuroendocrine carcinoma of ...

RNA viruses

Not all oncoviruses are

DNA virus A DNA virus is a virus that has a genome made of deoxyribonucleic acid (DNA) that is replicated by a DNA polymerase. They can be divided between those that have two strands of DNA in their genome, called double-stranded DNA (dsDNA) viruses, and ...

es. Some

RNA virus An RNA virus is a virusother than a retrovirusthat has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA ( ssRNA) but it may be double-stranded (dsRNA). Notable human diseases caused by RNA viruses ...

es have also been associated such as the

hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepato ...

as well as certain retroviruses, e.g.,

human T-lymphotropic virus The human T-lymphotropic virus, human T-cell lymphotropic virus, or human T-cell leukemia-lymphoma virus (HTLV) family of viruses are a group of human retroviruses that are known to cause a type of cancer called adult T-cell leukemia/lymphoma and ...

(HTLV-1) and Rous sarcoma virus (RSV).

Overview table

Estimated percent of new cancers attributable to the virus worldwide in 2002. NA indicates not available. The association of other viruses with human cancer is continually under research.

Main viruses associated with human cancer

The main viruses associated with human cancers are the

human papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...

, the

hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...

and

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...

viruses, the

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...

, the

human T-lymphotropic virus The human T-lymphotropic virus, human T-cell lymphotropic virus, or human T-cell leukemia-lymphoma virus (HTLV) family of viruses are a group of human retroviruses that are known to cause a type of cancer called adult T-cell leukemia/lymphoma and ...

, the

Kaposi's sarcoma-associated herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is ''Human gammaherpesvirus 8'', or HHV-8 in short. Like other herpesvirus ...

(KSHV) and the

Merkel cell polyomavirus Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called d ...

. 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 A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase ...

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 Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...

and

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...

, can induce a chronic viral infection that leads to

liver cancer Liver cancer (also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy) is cancer that starts in the liver. Liver cancer can be primary (starts in liver) or secondary (meaning cancer which has spread from elsewhere to th ...

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 is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form. The most common causes of viral hepatitis are the five unrelated hepatotropic v ...

transmission and disease. Through advances in cancer research, vaccines designed to prevent cancer have been created. The hepatitis B vaccine is the first vaccine that has been established to prevent cancer (

hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in t ...

) by preventing infection with the causative virus. In 2006, the

U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

approved a

human papilloma virus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...

vaccine, called

Gardasil Gardasil is an HPV vaccine for use in the prevention of certain strains of human papillomavirus (HPV). Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledge ...

. 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 The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...

(CDC)

Advisory Committee on Immunization Practices The Advisory Committee on Immunization Practices (ACIP) is a committee within the United States Centers for Disease Control and Prevention (CDC) that provides advice and guidance on effective control of vaccine-preventable diseases in the U.S. civ ...

(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.

History

The history of cancer virus discovery is intertwined with the

History of cancer The history of cancer describes the development of the field of oncology and its role in the history of medicine. Early diagnosis The earliest known descriptions of cancer appear in several papyri from Ancient Egypt. The Edwin Smith Papyrus was ...

research and the

history of virology The history of virology – the scientific study of viruses and the infections they cause – began in the closing years of the 19th century. Although Louis Pasteur and Edward Jenner developed the first vaccines to protect against viral infectio ...

. The oldest surviving record of a human cancer is the

Babylonia Babylonia (; Akkadian: , ''māt Akkadī'') was an ancient Akkadian-speaking state and cultural area based in the city of Babylon in central-southern Mesopotamia (present-day Iraq and parts of Syria). It emerged as an Amorite-ruled state c. ...

n

Code of Hammurabi The Code of Hammurabi is a Babylonian legal text composed 1755–1750 BC. It is the longest, best-organised, and best-preserved legal text from the ancient Near East. It is written in the Old Babylonian dialect of Akkadian, purportedly by Hamm ...

(dated ca. 1754 BC) but scientific

oncology Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ó ...

could only emerge in the 19th century, when

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s were studied at microscopic level with the help of the

compound microscope The optical microscope, also referred to as a light microscope, is a type of microscope that commonly uses visible light and a system of lenses to generate magnified images of small objects. Optical microscopes are the oldest design of microsco ...

and achromatic lenses. 19th century

microbiology Microbiology () is the scientific study of microorganisms, those being unicellular (single cell), multicellular (cell colony), or acellular (lacking cells). Microbiology encompasses numerous sub-disciplines including virology, bacteriology, prot ...

accumulated evidence that implicated bacteria,

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...

s, fungi, and

protozoa Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...

in the development of cancer. In 1926 the Nobel Prize was awarded for documenting that a nematode worm could provoke

stomach cancer Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymph ...

in rats. But it was not recognized that cancer could have infectious origins until much later as virus had first been discovered by

Dmitri Ivanovsky Dmitri Iosifovich Ivanovsky (alternative spelling ''Dmitrii'' or ''Dmitry Iwanowski''; russian: Дми́трий Ио́сифович Ивано́вский; 28 October 1864 – 20 June 1920) was a Russian botanist, the co-discoverer of :viruses ...

and

Martinus Beijerinck Martinus Willem Beijerinck (, 16 March 1851 – 1 January 1931) was a Dutch microbiologist and botanist who was one of the founders of virology and environmental microbiology. He is credited with the discovery of viruses, which he called "''c ...

at the close of the 19th century.

History of non-human oncoviruses

The theory that cancer could be caused by a virus began with the experiments of Oluf Bang and

Vilhelm Ellerman Vilhelm is a masculine given name, the Scandinavian languages, Scandinavian form of William (name), William and Wilhelm (name), Wilhelm. Notable people with the name include: * Vilhelm Ahlmann (1852-1928), Danish-Swedish architect * Vilhelm Anderse ...

in 1908 at the

University of Copenhagen The University of Copenhagen ( da, Københavns Universitet, KU) is a prestigious public university, public research university in Copenhagen, Copenhagen, Denmark. Founded in 1479, the University of Copenhagen is the second-oldest university in ...

. Bang and Ellerman demonstrated that

avian sarcoma leukosis virus Avian sarcoma leukosis virus (ASLV) is an endogenous retrovirus that infects and can lead to cancer in chickens; experimentally it can infect other species of birds and mammals. ASLV replicates in chicken embryo fibroblasts, the cells that contri ...

could be transmitted between chickens after cell-free filtration and subsequently cause leukemia. This was subsequently confirmed for solid tumors in chickens in 1910–1911 by

Peyton Rous Francis Peyton Rous () (October 5, 1879 – February 16, 1970) was an American pathologist at the Rockefeller University known for his works in oncoviruses, blood transfusion and physiology of digestion. A medical graduate from the Johns Hopki ...

. Rous at the

Rockefeller University The Rockefeller University is a private biomedical research and graduate-only university in New York City, New York. It focuses primarily on the biological and medical sciences and provides doctoral and postdoctoral education. It is classif ...

extended Bang and Ellerman's experiments to show cell-free transmission of a solid tumor sarcoma to chickens (now known as ''Rous sarcoma''). The reasons why chickens are so receptive to such transmission may involve unusual characteristics of stability or instability as they relate to

endogenous retroviruses Endogenous retroviruses (ERVs) are endogenous viral elements in the genome that closely resemble and can be derived from retroviruses. They are abundant in the genomes of jawed vertebrates, and they comprise up to 5–8% of the human genome (l ...

.

Charlotte Friend Charlotte Friend (March 11, 1921 – January 13, 1987) was an American virologist. She is best known for her discovery of the Friend leukemia virus. She helped to establish the concept of the oncovirus, studied the role of the host immune respon ...

confirmed Bang and Ellerman findings for

liquid tumor Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all ...

in mice by . In 1933

Richard Shope Richard Edwin Shope (December 25, 1901 – October 2, 1966) was an American virologist who, together with his mentor Paul A. Lewis at the Rockefeller Institute, identified influenzavirus A in pigs in 1931. Using Shope's technique, Smith, Andre ...

and

Edward Weston Hurst Edward is an English language, English given name. It is derived from the Old English, Anglo-Saxon name ''Ēadweard'', composed of the elements ''wikt:ead#Old English, ēad'' "wealth, fortune; prosperous" and ''wikt:weard#Old English, weard'' "gua ...

showed that

wart Warts are typically small, rough, hard growths that are similar in color to the rest of the skin. They typically do not result in other symptoms, except when on the bottom of the feet, where they may be painful. While they usually occur on the ...

s from wild

cottontail rabbit Cottontail rabbits are the leporid species in the genus ''Sylvilagus'', found in the Americas. Most ''Sylvilagus'' species have stub tails with white undersides that show when they retreat, giving them their characteristic name. However, this ...

s contained the

Shope papilloma virus The Shope papilloma virus (SPV), also known as cottontail rabbit papilloma virus (CRPV) or ''Kappapapillomavirus 2'', is a papillomavirus which infects certain leporids, causing keratinous carcinomas resembling horns, typically on or near the an ...

. In 1936

John Joseph Bittner John Joseph Bittner (February 25, 1904 – December 14, 1961) was a geneticist and cancer biologist, who made many contributions on the genetics of breast cancer research, which were of value, not only in cancer research, but also in a variety of ...

identified the

mouse mammary tumor virus Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus like the HTL viruses, HI viruses, and BLV. It belongs to the genus ''Betaretrovirus''. MMTV was formerly known as Bittner virus, and previously the "milk factor", referring to t ...

, an "extrachromosomal factor" (i.e. virus) that could be transmitted between laboratory strains of mice by breast feeding. 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 The Friend virus (FV) is a strain of murine leukemia virus identified by Charlotte Friend in 1957. The virus infects adult immunocompetent mice and is a well-established model for studying genetic resistance to infection by an immunosuppressive r ...

confirmed that

retroviral A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase e ...

integration could disrupt tumor suppressor genes, causing cancer. Viral

oncogenes An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

were subsequently discovered and identified to cause cancer.

Ludwik Gross Ludwik Gross (September 11, 1904 – July 19, 1999) was a Polish-American virologist who discovered two different tumor viruses—murine leukemia virus and mouse polyomavirus—capable of causing cancers in laboratory mice. Biography Gross was ...

identified the first mouse leukemia virus (

murine leukemia virus The murine leukemia viruses (MLVs or MuLVs) are retroviruses named for their ability to cause cancer in murine (mouse) hosts. Some MLVs may infect other vertebrates. MLVs include both exogenous and endogenous viruses. Replicating MLVs have a pos ...

) in 1951 and in 1953 reported on a component of mouse

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

extract capable of causing solid

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s in mice. This compound was subsequently identified as a virus by Sarah Stewart and

Bernice Eddy Bernice Eddy (September 30, 1903–May 24, 1989) was an American virologist and epidemiologist. She and Sarah Elizabeth Stewart are known for their discoveries related to polyomavirus, particularly SV40 polyomavirus. Personal life and education ...

at the

National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...

, after whom it was once called "SE polyoma". In 1957

Charlotte Friend Charlotte Friend (March 11, 1921 – January 13, 1987) was an American virologist. She is best known for her discovery of the Friend leukemia virus. She helped to establish the concept of the oncovirus, studied the role of the host immune respon ...

discovered the

Friend virus The Friend virus (FV) is a strain of murine leukemia virus identified by Charlotte Friend in 1957. The virus infects adult immunocompetent mice and is a well-established model for studying genetic resistance to infection by an immunosuppressive r ...

, a strain of murine leukemia virus capable of causing cancers in immunocompetent mice. Though her findings received significant backlash, they were eventually accepted by the field and cemented the validity of viral oncogenesis. In 1961 Eddy discovered the simian vacuolating virus 40 (

SV40 SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses, SV40 is a DNA virus that has the potential to cause tumors in animals, but most often ...

). Merck Laboratory also confirmed the existence of a rhesus macaque virus contaminating cells used to make Salk and Sabin polio vaccines. Several years later, it was shown to cause cancer in

Syrian hamster The golden hamster or Syrian hamster (''Mesocricetus auratus'') is a rodent belonging to the hamster subfamily, Cricetinae. Their natural geographical range is in an arid region of northern Syria and southern Turkey. Their numbers have been d ...

s, raising concern about possible human health implications. Scientific consensus now strongly agrees that this is not likely to cause human cancer.

History of human oncoviruses

In 1964

Anthony Epstein Sir Michael Anthony Epstein (born 18 May 1921) is a British pathologist and academic. He is one of the discoverers of the Epstein–Barr virus, along with Yvonne Barr and Bert Achong. Personal life Epstein was born on 18 May 1921, and educ ...

,

Bert Achong Bert Geoffrey Achong (6 December 1928 – 28 November 1996) was a Trinidadian-born pathologist known for co-discovering the Epstein–Barr virus through use of electron microscopy. Career Achong was born in Trinidad and Tobago and was of Chin ...

and

Yvonne Barr Yvonne Balding ( Barr; 11 March 1932 – 13 February 2016) was an Irish-born virologist who co-discovered the Epstein–Barr virus in 1964. Education and career Barr was born in Ireland: "Barr ..was born in Eire". and graduated with honours i ...

identified the first human oncovirus from

Burkitt's lymphoma Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa. ...

cells. A herpesvirus, this virus is formally known as human herpesvirus 4 but more commonly called

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...

or EBV. In the mid-1960s

Baruch Blumberg Baruch Samuel Blumberg (July 28, 1925 April 5, 2011), known as Barry Blumberg, was an American physician, geneticist, and co-recipient of the 1976 Nobel Prize in Physiology or Medicine (with Daniel Carleton Gajdusek), for his work on the hepat ...

first physically isolated and characterized

Hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...

while working at the

National Institute of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late 1 ...

(NIH) and later the

Fox Chase Cancer Center Fox Chase Cancer Center is a National Cancer Institute-designated Comprehensive Cancer Center research facility and hospital located in the Fox Chase section of Philadelphia, Pennsylvania, United States. The main facilities of the center are loca ...

. Although this agent was the clear cause of hepatitis and might contribute to liver cancer

hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in t ...

, this link was not firmly established until epidemiologic studies were performed in the 1980s by

R. Palmer Beasley Robert Palmer Beasley (April 29, 1936 – August 25, 2012) was a physician, public health educator and epidemiologist whose work on hepatitis B involved extensive investigations in Taiwan. That work established that hepatitis B virus (HBV) is a p ...

and others. In 1980 the first human retrovirus,

Human T-lymphotropic virus 1 Human T-cell lymphotropic virus type 1 or human T-lymphotropic virus (HTLV-I), also called the adult T-cell lymphoma virus type 1, is a retrovirus of the human T-lymphotropic virus (HTLV) family that has been implicated in several kinds of disea ...

(HTLV-I), was discovered by

Bernard Poiesz Bernard (''Bernhard'') is a French and West Germanic masculine given name. It is also a surname. The name is attested from at least the 9th century. West Germanic ''Bernhard'' is composed from the two elements ''bern'' "bear" and ''hard'' "brav ...

and

Robert Gallo Robert Charles Gallo (; born March 23, 1937) is an American biomedical researcher. He is best known for his role in establishing the human immunodeficiency virus (HIV) as the infectious agent responsible for acquired immune deficiency syndrome ( ...

at NIH, and independently by

Mitsuaki Yoshida was a Japanese virologist known for identifying the molecular structure of Human T-lymphotropic virus 1 responsible for Adult T-cell leukemia/lymphoma. Life Yoshida was born in Toyama, Japan and received his Ph.D. in 1967 from the University of ...

and coworkers in Japan. But it was not certain whether HTLV-I promoted leukemia. In 1981 Yorio Hinuma and his colleagues at

Kyoto University , mottoeng = Freedom of academic culture , established = , type = National university, Public (National) , endowment = ¥ 316 billion (2.4 1000000000 (number), billion USD) , faculty = 3,480 (Teaching Staff) , administrative_staff ...

reported visualization of retroviral particles produced by a leukemia cell line derived from patients with

Adult T-cell leukemia/lymphoma Adult T-cell leukemia/lymphoma (ATL or ATLL) is a rare cancer of the immune system's T-cells caused by human T cell leukemia/lymphotropic virus type 1 (HTLV-1). All ATL cells contain integrated HTLV-1 provirus further supporting that causal role o ...

. This virus turned out to be HTLV-1 and the research established the causal role of the HTLV-1 virus to ATL. 15 Hegasy Nobel Prize 2020 HepC

Between 1984 and 1986

Harald zur Hausen Harald zur Hausen NAS EASA APS (; born 11 March 1936) is a German virologist and professor emeritus. He has done research on cervical cancer and discovered the role of papilloma viruses in cervical cancer, for which he received the Nobe ...

and

Lutz Gissmann Lutz Gissmann (born September 18, 1949 in Kaufbeuren, Germany) is a German virologist and was head of the Division “Genome Modifications and Carcinogenesis” at the German Cancer Research Center (DKFZ) in Heidelberg until his retirement in 2015 ...

discovered HPV16 and HPV18, together these

Papillomaviridae ''Papillomaviridae'' is a family of non- enveloped DNA viruses whose members are known as papillomaviruses. Several hundred species of papillomaviruses, traditionally referred to as "types", have been identified infecting all carefully inspected ...

viruses (HPV) are responsible for approximately 70% of

human papillomavirus infection Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...

s that cause

cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...

s. For the discovery that HPV cause human cancer the 2008 Nobel Prize was awarded. In 1987 the

Hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepato ...

(HCV) was discovered by panning a cDNA library made from diseased tissues for foreign antigens recognized by patient sera. This work was performed by Michael Houghton at

Chiron In Greek mythology, Chiron ( ; also Cheiron or Kheiron; ) was held to be the superlative centaur amongst his brethren since he was called the "wisest and justest of all the centaurs". Biography Chiron was notable throughout Greek mythology ...

, a biotechnology company, and

Daniel W. Bradley Daniel W. Bradley (born 13 July 1941) is an important American virologist who, along with Michael Houghton, Qui-Lim Choo and George Kuo at Chiron Corporation, worked to help isolate the Hepatitis C virus in 1989. He graduated from San José Stat ...

at the

Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...

(CDC). HCV was subsequently shown to be a major contributor to

Hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in t ...

(liver cancer) worldwide. In 1994

Patrick S. Moore Patrick S. Moore (born October 21, 1956) is an Irish and 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 ...

and

Yuan Chang Yuan Chang (; born 17 November 1959) is a Taiwanese-American virologist and pathologist who co-discovered together with her husband, Patrick S. Moore, the Kaposi's sarcoma-associated herpesvirus (KSHV) and Merkel cell polyomavirus, two of the s ...

at

Columbia University Columbia University (also known as Columbia, and officially as Columbia University in the City of New York) is a private research university in New York City. Established in 1754 as King's College on the grounds of Trinity Church in Manhatt ...

), working together with

Ethel Cesarman Ethel (also '' æthel'') is an Old English word meaning "noble", today often used as a feminine given name. Etymology and historic usage The word means ''æthel'' "noble". It is frequently attested as the first element in Anglo-Saxon names, b ...

, isolated

Kaposi's sarcoma-associated herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is ''Human gammaherpesvirus 8'', or HHV-8 in short. Like other herpesvirus ...

(KSHV or HHV8) using

representational difference analysis Representational difference analysis (RDA) is a technique used in biological research to find sequence differences in two genomic or cDNA samples. Genomes or cDNA sequences from two samples (i.e. cancer sample and a normal sample) are PCR amplifi ...

. This search was prompted by work from

Valerie Beral Dame Valerie Beral AC DBE FRS FRCOG FMedSci (28 July 1946 – 26 August 2022) was an Australian-born British epidemiologist, academic and a preeminent specialist in breast cancer epidemiology. She was Professor of Epidemiology, a Fellow of ...

and colleagues who inferred from the epidemic of

Kaposi's sarcoma Kaposi's sarcoma (KS) is a type of cancer that can form masses in the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limite ...

among patients with AIDS that this cancer must be caused by another infectious agent besides HIV, and that this was likely to be a second virus. Subsequent studies revealed that KSHV is the "KS agent" and is responsible for the epidemiologic patterns of KS and related cancers. In 2008

Yuan Chang Yuan Chang (; born 17 November 1959) is a Taiwanese-American virologist and pathologist who co-discovered together with her husband, Patrick S. Moore, the Kaposi's sarcoma-associated herpesvirus (KSHV) and Merkel cell polyomavirus, two of the s ...

and

Patrick S. Moore Patrick S. Moore (born October 21, 1956) is an Irish and 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 ...

developed a new method to identify cancer viruses based on computer subtraction of human sequences from a tumor

transcriptome The transcriptome is the set of all RNA transcripts, including coding and non-coding, in an individual or a population of cells. The term can also sometimes be used to refer to all RNAs, or just mRNA, depending on the particular experiment. The t ...

, called digital transcriptome subtraction (DTS). DTS was used to isolate DNA fragments of

Merkel cell polyomavirus Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called d ...

from a Merkel cell carcinoma and it is now believed that this virus causes 70–80% of these cancers.

References

External links

* {{Authority control Carcinogenesis Virology Viruses Infectious causes of cancer

Causality

Oncogenic viral mechanism

DNA oncoviruses

Integration of viral DNA

G1/S Checkpoint

Inactivation of p53

Inactivation of Rb

Variations

RNA oncoviruses

Description of virus

Retrovirus enters host cell

Classification

DNA viruses

RNA viruses

Overview table

Main viruses associated with human cancer

History

History of non-human oncoviruses

History of human oncoviruses

See also

References

External links