Phosphorylation of human polyomavirus BK agnoprotein at Ser-11 is mediated by PKC and has an important regulative function

Johannessen, Mona; Myhre, Marit Renée; Dragset, Marte Singsås; Tümmler, Conny; Moens, Ugo

doi:10.1016/j.virol.2008.06.007

Cited by 34 publications

(52 citation statements)

References 61 publications

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“…Single or combinatorial mutations at these sites converted JCV in an essentially nonfunctional virus after the first round of replication cycle (Sariyer et al, 2006). Similar work by Johannessen et al, demonstrated the functional importance of the phosphorylated forms of agnoprotein for BKV replication cycle (Johannessen et al, 2008). Analysis of a deletion mutant of BKV agnoprotein by Myhre et al, also showed that BKV has a restricted life cycle in the absence of agnoprotein, but viral function can be rescued when native agnoprotein is provided in trans (Myhre et al, 2010).…”

Section: Discussionmentioning

confidence: 61%

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Human polyomavirus JC small regulatory agnoprotein forms highly stable dimers and oligomers: Implications for their roles in agnoprotein function

et al. 2011

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JC virus (JCV) encodes a small basic phosphoprotein from the late coding region called agnoprotein, which has been shown to play important regulatory roles in the viral replication cycle. In this study, we report that agnoprotein forms highly stable dimers and higher order oligomer complexes. This was confirmed by immunoblotting and mass spectrometry studies. These complexes are extremely resistant to strong denaturing agents, including urea and SDS. Central portion of the protein, amino acids spanning from 17 to 42 is important for dimer/oligomer formation. Removal of 17 to 42 aa region from the viral background severely affected the efficiency of the JCV replication. Extracts prepared from JCV-infected cells showed a double banding pattern for agnoprotein in vivo. Collectively, these findings suggest that agnoprotein forms functionally active homodimer/oligomer complexes and these may be important for its function during viral propagation and thus for the progression of PML.

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Section: Discussionmentioning

confidence: 61%

“…This modification plays a significant role in the function of this protein during the viral replication cycle of BK virus and JC virus (Johannessen et al, 2008; Sariyer et al, 2006). SV40 agnoprotein was also previously reported to be phosphorylated but no function was assigned to it (Nomura, Khoury, and Jay, 1983).…”

Section: Introductionmentioning

confidence: 99%

Human polyomavirus JC small regulatory agnoprotein forms highly stable dimers and oligomers: Implications for their roles in agnoprotein function

et al. 2011

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“…Agnoprotein is a 71 aa multi-functional protein with numerous reported protein-protein interactions (Darbinyan et al, 2004;Endo et al, 2003;Johannessen et al, 2008;Safak et al, 2002;Suzuki et al, 2005). It also retains a central hydrophobic TMD which, along with an N-terminal region, is required for ER/plasma membrane localization and membrane integration (Suzuki et al, 2010), and forms stable oligomers within infected cells (Coric et al, 2014;Saribas et al, 2011Saribas et al, , 2013Suzuki et al, 2010).…”

Section: Dna Virus Viroporinsmentioning

confidence: 99%

Viroporins: structure, function and potential as antiviral targets

Scott

Griffin

2015

Journal of General Virology

124

146

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The channel-forming activity of a family of small, hydrophobic integral membrane proteins termed 'viroporins' is essential to the life cycles of an increasingly diverse range of RNA and DNA viruses, generating significant interest in targeting these proteins for antiviral development. Viroporins vary greatly in terms of their atomic structure and can perform multiple functions during the virus life cycle, including those distinct from their role as oligomeric membrane channels. Recent progress has seen an explosion in both the identification and understanding of many such proteins encoded by highly significant pathogens, yet the prototypic M2 proton channel of influenza A virus remains the only example of a viroporin with provenance as an antiviral drug target. This review attempts to summarize our current understanding of the channel-forming functions for key members of this growing family, including recent progress in structural studies and drug discovery research, as well as novel insights into the life cycles of many viruses revealed by a requirement for viroporin activity. Ultimately, given the successes of drugs targeting ion channels in other areas of medicine, unlocking the therapeutic potential of viroporins represents a valuable goal for many of the most significant viral challenges to human and animal health.

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“…Like that of JCV, phosphorylation of BKV agnoprotein at Ser-11 by PKC has also been recently reported to have an important regulatory function (50). Additional recent studies have continued to explore the regulation of BKV at the level of transcriptional control of the NCCR, in particular the notion that cytokines, and the transcription factors that lie downstream of them, may be involved in the regulation of the balance between BKV latency and reactivation.…”

Section: Recent Studies Of Primate Polyomavirusesmentioning

confidence: 99%

Regulation of Gene Expression in Primate Polyomaviruses

White

Safak

Khalili

2009

J Virol

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Polyomaviruses are a growing family of small DNA viruses with a narrow tropism for both the host species and the cell type in which they productively replicate. Species host range may be constrained by requirements for precise molecular interactions between the viral T antigen, host replication proteins, including DNA polymerase, and the viral origin of replication, which are required for viral DNA replication. Cell type specificity involves, at least in part, transcription factors that are necessary for viral gene expression and restricted in their tissue distribution. In the case of the human polyomaviruses, BK virus (BKV) replication occurs in the tubular epithelial cells of the kidney, causing nephropathy in kidney allograft recipients, while JC virus (JCV) replication occurs in the glial cells of the central nervous system, where it causes progressive multifocal leukoencephalopathy. Three new human polyomaviruses have recently been discovered: MCV was found in Merkel cell carcinoma samples, while Karolinska Institute Virus and Washington University Virus were isolated from the respiratory tract. We discuss control mechanisms for gene expression in primate polyomaviruses, including simian vacuolating virus 40, BKV, and JCV. These mechanisms include not only modulation of promoter activities by transcription factor binding but also enhancer rearrangements, restriction of DNA methylation, alternate early mRNA splicing, cis-acting elements in the late mRNA leader sequence, and the production of viral microRNA.Polyomaviruses comprise a family of small nonenveloped DNA tumor viruses which have small, circular, doublestranded DNA genomes, have been isolated from many species of mammals and birds, and are characterized by a very limited host range with respect to the species that they can productively infect (48). We will focus mainly on three primate viruses, simian vacuolating virus 40 (SV40), BK virus (BKV), and JC virus (JCV), not only because they have taught us important lessons about eukaryotic molecular biology but also because BKV and JCV cause important human diseases. SV40 was discovered almost 50 years ago (115) and was the first primate polyomavirus to be described. SV40 differs significantly from the previously discovered mouse polyoma virus (111) in that it does not possess a middle T antigen in the early region and it expresses an accessory regulatory protein, agnoprotein, which is encoded in the late region. The species of origin of SV40 is the rhesus macaque, and the virus was discovered as a contaminant in early batches of polio vaccine. While the polio vaccinations at that time likely infected many people, the prevalence of SV40 infections in humans today has been debated (36,122). In 1971, two bona fide human polyomaviruses were discovered. BKV, also known as polyomavirus BK, was first isolated by Gardner et al. (37) by culture in Vero cells from the urine of a patient receiving immunosuppressive therapy following kidney transplantation. BKV is widespread throughout the human population around...

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Phosphorylation of human polyomavirus BK agnoprotein at Ser-11 is mediated by PKC and has an important regulative function

Cited by 34 publications

References 61 publications

Human polyomavirus JC small regulatory agnoprotein forms highly stable dimers and oligomers: Implications for their roles in agnoprotein function

Human polyomavirus JC small regulatory agnoprotein forms highly stable dimers and oligomers: Implications for their roles in agnoprotein function

Viroporins: structure, function and potential as antiviral targets

Regulation of Gene Expression in Primate Polyomaviruses

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