Polyomaviruses and human cancer: molecular mechanisms underlying patterns of tumorigenesis

White, Martyn K.; Khalili, Kamel

doi:10.1016/j.virol.2004.03.025

Cited by 142 publications

(156 citation statements)

References 146 publications

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“…However, when the same positive samples were tested for the presence of the early region of the viral genome, an amplified product was obtained only in four of the KIV-VP1 positive cases. This apparent discrepant result might be explained by the nucleotide variability observed in the C-terminal part of T-Ag gene of polyomaviruses [Lednicky et al, 1997;White and Khalili, 2004].…”

Section: Discussionmentioning

confidence: 98%

“…The human polyomaviruses BKV and JCV have been detected in several human tumors [White and Khalili, 2004;Giuliani et al, 2008] including the respiratory tract [Giuliani et al, 2007;Zheng et al, 2007], and induce tumors in animal models [Sariyer et al, 2004]. This prompted us to investigate the presence of KIV in normal and malignant respiratory tissue.…”

Section: Discussionmentioning

confidence: 99%

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Identification of the novel KI Polyomavirus in paranasal and lung tissues

Babakir‐Mina¹,

Ciccozzi

Campitelli

et al. 2009

Journal of Medical Virology

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KI is a novel polyomavirus identified in the respiratory secretions of children with acute respiratory symptoms. Whether this reflects a causal role of the virus in the human respiratory disease remains to be established. To investigate the presence of KIV in the respiratory tissue, we examined 20 fresh lung cancer specimens and surrounding normal tissue along with one paranasal and one lung biopsy from two transplanted children. KIV‐VP1 gene was detected in 9/20 lung cancer patients and 2/2 transplanted patients. However, amplification of the sequence coding for the C‐terminal part of the early region of KIV performed on the 11 positive cases was successful only in two malignant lung tissues, one surrounding normal tissue, and 1/2 biopsies tested. Phylogenetic analysis performed on the early region of KIV (including the four Italian isolates), BKV and JCV revealed the presence of three distinct clades. Within the KIV clade two sub‐clades were observed. A sub‐clade A containing the four Italian strains, and a sub‐clade B comprising the Swedish and Australian isolates. Interestingly, the two Italian strains identified in normal tissue clustered together, whereas those detected in malignant tissue fell outside this cluster. In vitro studies are needed to investigate the transforming potential of KIV strains. J. Med. Virol. 81:558–561, 2009. © 2009 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Identification of the novel KI Polyomavirus in paranasal and lung tissues

Babakir‐Mina¹,

Ciccozzi

Campitelli

et al. 2009

Journal of Medical Virology

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“…RNase-L activation induces premature senescence Ectopic RNase-L expression induced distinct responses of senescence in HDFs (Figure 2) and apoptosis in established cell lines (Castelli et al, 1997) that may reflect a fundamental difference in the response of primary and immortalized cells to antiproliferative stimuli. To determine if RNase-L activation by exogenous 2-5A induced senescence in primary HDFs, and if this response differed in SV40-immortalized cells in which the critical senescence mediators p53 and pRb are inactivated (White and Khalili, 2004), 2-5A was transfected into parental and SV-WI38 cells. Remarkably, 2-5A transfection of primary WI38 HDFs induced a dose-dependent, eightfold increase in b-gal staining (Figure 4a and b), indicating that primary HDFs remain viable, albeit senescent, following RNase-L activation.…”

Section: Rnase-l Expression Induces a Senescent Phenotypementioning

confidence: 99%

Role of 2-5A-dependent RNase-L in senescence and longevity

Andersen

Judge

et al. 2006

Oncogene

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Senescence is a permanent growth arrest that restricts the lifespan of primary cells in culture, and represents an in vitro model for aging. Senescence functions as a tumor suppressor mechanism that can be induced independent of replicative crisis by diverse stress stimuli. RNase-L mediates antiproliferative activities and functions as a tumor suppressor in prostate cancer, therefore, we examined a role for RNase-L in cellular senescence and aging. Ectopic expression of RNase-L induced a senescent morphology, a decrease in DNA synthesis, an increase in senescence-associated b-galactosidase activity, and accelerated replicative senescence. In contrast, senescence was retarded in RNase-L-null fibroblasts compared with wildtype fibroblasts. Activation of endogenous RNase-L by 2-5A transfection induced distinct senescent and apoptotic responses in parental and Simian virus 40-transformed WI38 fibroblasts, respectively, demonstrating cell type specific differences in the antiproliferative response to RNase-L activation. Replicative senescence is a model for in vivo aging; therefore, genetic disruption of senescence effectors may impact lifespan. RNase-L À/À mice survived 31.7% (Po0.0001) longer than strain-matched RNase-L +/+ mice providing evidence for a physiological role for RNase-L in aging. These findings identify a novel role for RNase-L in senescence that may contribute to its tumor suppressive function and to the enhanced longevity of RNase-L À/À mice.

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“…Three polyomaviruses have been described in humans: JCV, BKV and SV40. All three viruses transform cells in culture and are highly oncogenic in experimental animals and may be associated with some clinical tumors (reviewed in White and Khalili, 2004a;. JCV is a neurotropic polyomavirus, that is the proven etiologic agent of progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system occurring in immunocompromised individuals, mainly AIDS patients .…”

Section: Human Polyomavirusesmentioning

confidence: 99%

“…However, in non-permissive cells, infection is abortive and cellular transformation may occur. The phenotypic features of cellular transformation in cell culture, the production of tumors in experimental animals and the association of polyomaviruses with clinical tumors have been reviewed recently (White and Khalili, 2004a;. Transformation requires expression of the early region, in particular the large T-antigen.…”

Section: Human Polyomavirusesmentioning

confidence: 99%

Interaction of retinoblastoma protein family members with large T-antigen of primate polyomaviruses

White

Khalili

2006

Oncogene

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The retinoblastoma gene product pRb and other members of the Rb family of pocket proteins have a central role in the regulation of cell cycle progression. Soon after its discovery, pRb was found to interact with the transforming oncoproteins of DNA tumor viruses and this led to rapid advances in our understanding of the mechanisms of viral transformation and cell cycle progression. DNA viruses of the polyomavirus family have small, circular, double-stranded DNA genomes contained within nonenveloped icosahedral capsids and are highly tumorigenic in experimental animals. At least three types of polyomavirus infect humans: JC virus (JCV), BK virus (BKV) and Simian Vacuolating virus-40. The early region of these viruses encodes the transforming proteins large T-antigen and small t-antigen, which are involved in viral replication and also promote transformation of cells in culture and oncogenesis in vivo. Binding of T-antigen to pRb promotes the activation of the E2F family of transcription factors, which induce the expression of cellular genes required for S phase. In the context of lytic infection, this cell cycle progression is necessary for viral replication because polyomaviruses rely on S phasespecific host factors for their DNA synthesis. In the context of cellular transformation and tumorigenesis, T-antigen/pRB interaction is an indispensable event.

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Polyomaviruses and human cancer: molecular mechanisms underlying patterns of tumorigenesis

Cited by 142 publications

References 146 publications

Identification of the novel KI Polyomavirus in paranasal and lung tissues

Identification of the novel KI Polyomavirus in paranasal and lung tissues

Role of 2-5A-dependent RNase-L in senescence and longevity

Interaction of retinoblastoma protein family members with large T-antigen of primate polyomaviruses

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