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Simian Virus 40, or SV-40
Simian Virus 40, or SV-40, is a small double stranded, circular DNA virus of rhesus monkey origin. It is closely related to JC and BK viruses of human origin. While BK virus may not cause human disease, JC virus can cause a very severe brain illness in HIV infected patients, which is called progressive multifocal leukoencephalopathy or PML. SV-40 is also distantly related to human papillomaviruses, some of which cause cervical cancers. (Ref. Dr. W. John Martin www.ccid.org)
SV-40 is classified as a polyomavirus, as are BK virus (BKV) and JC virus (JCV). Polyomaviruses are members of the Papovaviridae family, which are small, nonenveloped viruses with a closed, circular double DNA-stranded genome. Polyomaviruses are ubiquitous in nature and can be isolated from a number of species.1 All 3 viruses typically establish persistent, subclinical infections in their hosts, and they share the capacity for reactivation from latency when the host is immunocompromised.
SV-40 is asymptomatic in monkeys, however it does transform cultured human cells and does produce tumors when injected into newborn rodents.4 SV-40 DNA has been discovered in human tumors, specifically in mesotheliomas, brain tumors, osteosarcomas, choroids plexus tumors and ependyomas.4 The presence of SV-40 in human mesotheliomas and other human tumors has been confirmed by the work of more than 26 research groups.
Prior to reviewing recent molecular findings with mesothelioma, it is important to discuss the role of SV40 in mesothelioma. SV40 is a DNA tumor virus with transforming ability that contaminated polio and adenovirus vaccines in the 1950’s and 1960’s. Seroprevalence of SV40 varies from 2 to 20% worldwide. SV40 infection is highest among immune suppressed and compromised individuals. SV40 is found in both adults and children and is thought to be transmitted via maternal-fetal and oral-fecal routes. The SV40 large tumor antigen (T-ag) stimulates host cells to replicate by entering into the S phase of the cell cycle, and is considered the major SV40 transforming protein. This protein binds and inactivates several tumor suppressor genes (p53, Rb) that are responsible for regulation of the cell cycle.
SV40 T-ag is found in a high proportion of mesotheliomas (about 50%), primary brain tumors (21%), non-Hodgkins lymphomas (36%) and osteosarcomas (Table 3). Of particular interest to mesothelioma development, normal mesothelial cell cultures transform readily when infected with SV40. This appears to be related to inactivation of cell regulatory genes by the SV40 T-ag protein (p53, RASSFIA tumor suppressor genes). Other cell signaling and transduction factors are also upregulated (Notch-1, met).
SV-40 infection is now widespread within the human population almost certainly as a result of poliovaccine produced in rhesus monkey kidney cells during the 1950s. A recent study showed infection in 23% of blood samples from normal individuals. The virus can also be detected in sperm fluid and is likely to be passed congenitally to future generations (Martini et al. SV40 Early Region and Large T Antigen in Human Brain Tumors, Peripheral Blood Cells, and Sperm Fluids from Healthy Individuals. Cancer Research 56: 4820-4825, 1996).
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