BK virus and human cancer: Innocent until proven guilty

Abend, Johanna R.; Jiang, Mengxi; Imperiale, Michael J.

doi:10.1016/j.semcancer.2009.02.004

Cited by 115 publications

(111 citation statements)

References 143 publications

(123 reference statements)

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“…For example, like EBV, the human neurotropic polyomavirus JC virus sometimes can replicate to high levels in patients immunosuppressed by HIV/AIDS, with high TGF-␤ levels inducing JC virus-infected cells to produce infectious virus (18,61,68). Likewise, BK virus, another human polyomavirus, is frequently reactivated following kidney transplantation and immunosuppressant drug therapy (2). Elevated levels of TGF-␤ are observed after treatment with immunosuppressive drugs such as cyclosporine.…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor β-Induced Reactivation of Epstein-Barr Virus Involves Multiple Smad-Binding Elements Cooperatively Activating Expression of the Latent-Lytic SwitchBZLF1Gene

Iempridee

Das

et al. 2011

J Virol

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Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor β-Induced Reactivation of Epstein-Barr Virus Involves Multiple Smad-Binding Elements Cooperatively Activating Expression of the Latent-Lytic SwitchBZLF1Gene

Iempridee

Das

et al. 2011

J Virol

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“…Since then, 6 additional human polyomaviruses have been discovered, including HPyV6, HPyV7, TSPyV, HPyV9, MWPyV, and STLPyV (10)(11)(12)(13)(14)(15). Although JCPyV and BKPyV have been detected in a variety of human cancers (16,17), Merkel cell polyomavirus is the only polyomavirus DNA clonally integrated in human cancer. Expression of Merkel large and small T antigens can be detected in most MCC specimens (5,18,19).…”

mentioning

confidence: 99%

Merkel Cell Polyomavirus Large T Antigen Has Growth-Promoting and Inhibitory Activities

Cheng

Rozenblatt-Rosen

Paulson

et al. 2013

J Virol

103

144

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cMerkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. In at least 80% of all MCC, Merkel cell polyomavirus (MCPyV) DNA has undergone clonal integration into the host cell genome, and most tumors express the MCPyV large and small T antigens. In all cases of MCC reported to date, the integrated MCPyV genome has undergone mutations in the large T antigen. These mutations result in expression of a truncated large T antigen that retains the Rb binding or LXCXE motif but deletes the DNA binding and helicase domains. However, the transforming functions of full-length and truncated MCPyV large T antigen are unknown. We compared the transforming activities of full-length, truncated, and alternatively spliced 57kT forms of MCPyV large T antigen. MCPyV large T antigen could bind to Rb but was unable to bind to p53. Furthermore, MCPyV-truncated large T antigen was more effective than full-length and 57kT large T antigen in promoting the growth of human and mouse fibroblasts. In contrast, expression of the MCPyV large T antigen C-terminal 100 residues could inhibit the growth of several different cell types. These data imply that the deletion of the C terminus of MCPyV large T antigen found in MCC serves not only to disrupt viral replication but also results in the loss of a distinct growth-inhibitory function intrinsic to this region. Merkel cell carcinoma (MCC) is an aggressive skin cancer with an annual incidence of 3 per million in the United States (1). Risk factors for developing MCC include advanced age, prolonged UV exposure, and immunosuppression due to HIV, hematologic malignancy, or solid-organ transplantation (2, 3). Recently, Merkel cell polyomavirus (MCPyV) was discovered to be clonally integrated in at least 80% of MCC, raising the possibility that this pathogen contributes to carcinogenesis (4, 5).MCPyV is a typical polyomavirus with a circular, doublestranded DNA genome containing an early region that expresses large and small T antigens, a late region that encodes 3 viral coat proteins, VP1, VP2, and VP3, and a regulatory region that contains the origin of replication and a bidirectional promoter for the early and late genes. MCPyV was the fifth polyomavirus identified in humans, preceded by BKPyV, JCPyV, KIPyV, and WUPyV (6-9). Since then, 6 additional human polyomaviruses have been discovered, including HPyV6, HPyV7, TSPyV, HPyV9, MWPyV, and STLPyV (10-15). Although JCPyV and BKPyV have been detected in a variety of human cancers (16, 17), Merkel cell polyomavirus is the only polyomavirus DNA clonally integrated in human cancer. Expression of Merkel large and small T antigens can be detected in most MCC specimens (5, 18, 19).The T antigens from several polyomaviruses have oncogenic activity. Notably, the simian virus 40 (SV40) large and small T antigens can transform a variety of rodent and human cells. Expression of SV40 large and small T antigens, together with human telomerase reverse transcriptase and an oncogenic form of H-RAS, can fully transform normal human fibroblasts (20,21)...

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“…However, due to conflicting results regarding the detection of specific sequences and proteins in human cancers, the oncogenic role of this virus remains controversial. 72 Profound immunological impairment, like that experienced by transplant organ recipients, may be necessary for BKV reactivation. Virus replication has been associated with a number of diseases, such as hemorrhagic cystitis, ureteric stenosis and PVAN, but the potential association of BKV infection with malignancy, particularly of urothelial and renal tubular origin, is still being debated.…”

Section: Bkv and Human Tumorsmentioning

confidence: 99%

A Potential Linkage Between the JC and BK Polyomaviruses and Brain and Urinary Tract Tumors: A Review of the Literature

Carluccio¹,

Signorini²,

Elia³

et al. 2014

Advances in Tumor Virology

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JC virus (JCV) and BK virus (BKV) belong to the Polyomaviridae family and were the first human polyomaviruses (PyVs) discovered. Both JCV and BKV remain latent in the kidneys and can reactivate in immunocompromised hosts, causing progressive multifocal leukoencephalopathy (PML) and nephropathy, respectively. PyVs induce cell transformation in vitro and in animal models, where they infect non-permissive cells. The molecular mechanisms of tumor formation are based on the large tumor antigen (T Ag) protein, which is able to bind and inactivate pRb and p53, inducing uncontrolled cell cycle progression. Many studies on clinical samples also indicate a positive association between JCV and BKV and human solid tumors; however no direct involvement of PyVs in the development of human cancers has been demonstrated. In this review we focused on the potential association between JCV and BKV with brain and urinary tract tumors, respectively.

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BK virus and human cancer: Innocent until proven guilty

Cited by 115 publications

References 143 publications

Transforming Growth Factor β-Induced Reactivation of Epstein-Barr Virus Involves Multiple Smad-Binding Elements Cooperatively Activating Expression of the Latent-Lytic SwitchBZLF1Gene

Transforming Growth Factor β-Induced Reactivation of Epstein-Barr Virus Involves Multiple Smad-Binding Elements Cooperatively Activating Expression of the Latent-Lytic SwitchBZLF1Gene

Merkel Cell Polyomavirus Large T Antigen Has Growth-Promoting and Inhibitory Activities

A Potential Linkage Between the JC and BK Polyomaviruses and Brain and Urinary Tract Tumors: A Review of the Literature

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