The Presumed Polyomavirus Viroporin VP4 of Simian Virus 40 or Human BK Polyomavirus Is Not Required for Viral Progeny Release

Polyomavirus family consists of a highly diverse group of small DNA viruses. The founding family member (MPyV) was first discovered in the newborn mouse in the late 1950s, which induces solid tumors in a wide variety of tissue types that are the epithelial and mesenchymal origin. Later, other family members were also isolated from a number of mammalian, avian and fish species. Some of these viruses significantly contributed to our current understanding of the fundamentals of modern biology such as transcription, replication, splicing, RNA editing, and cell transformation. After the discovery of first two human polyomaviruses (JC virus [JCV] and BK virus [BKV]) in the early 1970s, there has been a rapid expansion in the number of human polyomaviruses in recent years due to the availability of the new technologies and brought the present number to 14. Some of the human polyomaviruses cause considerably serious human diseases, including progressive multifocal leukoencephalopathy, polyomavirus‐associated nephropathy, Merkel cell carcinoma, and trichodysplasia spinulosa. Emerging evidence suggests that the expression of the polyomavirus genome is more complex than previously thought. In addition to encoding universally expressed regulatory and structural proteins (LT‐Ag, Sm t‐Ag, VP1, VP2, and VP3), some polyomaviruses express additional virus‐specific regulatory proteins and microRNAs. This review summarizes the recent advances in polyomavirus genome expression with respect to the new viral proteins and microRNAs other than the universally expressed ones. In addition, a special emphasis is devoted to the recent structural and functional discoveries in the field of polyomavirus agnoprotein which is expressed only by JCV, BKV, and simian virus 40 genomes.

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“…| 8299 also suggests that VP4 is not required for the release of BKV from the infected cells (Henriksen, Hansen, Bruun, & Rinaldo, 2016).…”

Section: Expression Of the Late Coding Region Of Polyomavirusesmentioning

confidence: 99%

Expression of novel proteins by polyomaviruses and recent advances in the structural and functional features of agnoprotein of JC virus, BK virus, and simian virus 40

Sarıbaş

Coric

Bouaziz

et al. 2018

Journal Cellular Physiology

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“…VP4 is a late SV40 protein previously reported to function as a viroporin to support virus release which disrupted membranes when ectopically added to red blood cells, liposomes or Cos-7 cells (35). However, more recent studies did not confirm the lytic activity of VP4 during SV40 infection (15). In the context of SV40 replication, the expression of VP1 alone, without VP2 and VP3, leads to cell lysis and the release of viral particles, suggesting that lytic activity is mediated via VP1, likely through activation of a cellular program as reported here (14, 15).…”

Section: Discussionmentioning

confidence: 96%

“…However, more recent studies did not confirm the lytic activity of VP4 during SV40 infection (15). In the context of SV40 replication, the expression of VP1 alone, without VP2 and VP3, leads to cell lysis and the release of viral particles, suggesting that lytic activity is mediated via VP1, likely through activation of a cellular program as reported here (14, 15).…”

Section: Discussionmentioning

confidence: 96%

“…Viral proteins have been reported to facilitate SV40 release from cells. The late protein VP4 was reported to function as a viroporin with membrane-destabilizing properties that facilitates virus release, but these results have recently been challenged (14, 15). Furthermore, since VP4 is mostly found within the nucleus of infected cells, the mechanism leading to plasma membrane perforation and virus release is unclear.…”

Section: Introductionmentioning

confidence: 99%

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SV40 polyomavirus activates the Ras-MAPK signaling pathway for vacuolization, cell death, and virus release

Motamedi

Sewald

Luo

et al. 2018

Preprint

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26Polyomaviruses are a family of small, non-enveloped DNA viruses that can cause severe 27 disease in immunosuppressed individuals. Studies with SV40, a well-studied model 28 polyomavirus, have revealed the role of host proteins in polyomavirus entry and trafficking to 29 the nucleus, viral transcription and DNA replication, and cell transformation. In contrast, little 30 is known about host factors or cellular signaling pathways involved in the late steps of 31 productive infection leading to polyomavirus release. We previously showed that cytoplasmic 32 vacuolization, a characteristic late cytopathic effect of SV40, depends on the specific 33 interaction between the major viral capsid protein VP1 and its cell surface ganglioside 34 receptor GM1. Here we show that late during infection, SV40 activates a signaling cascade in 35 permissive CV-1 monkey cells involving Ras, Rac1, MKK4 and JNK to induce SV40-specific 36 cytoplasmic vacuolization and subsequent cell lysis and virus release. Inhibition of individual 37 components of this signaling pathway inhibits vacuolization, lysis and virus release, even 38 though high-level intracellular virus replication occurs. The identification of this pathway for 39 SV40-induced vacuolization and virus release provides new insights into the late steps of non-40 enveloped virus infection and reveals potential drug targets for the treatment of diseases 41 caused by these viruses. 42 43 -3-

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“…Later, Vp4 was described to be a viroporin, forming aqueous pores that increased the membrane permeability (4)(5)(6). Based upon citations in papers and virology textbooks, the existence of SV40 Vp4 seems to be widely accepted, despite the conflicting data from independent research groups (7,8).…”

mentioning

confidence: 99%

Does the Evidence Support the Existence of the Simian Polyomavirus SV40 Vp4 Viroporin?

Henriksen

Rinaldo

2020

mSphere

Self Cite

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The simian polyomavirus SV40 was reported to express Vp4, an N-terminally truncated form of the minor capsid proteins Vp2 and Vp3. Since a missense mutation of the putative Vp4 start codon (Vp2M228I) was found to give reduced progeny release and delayed lysis, Vp4 was claimed to be a viroporin. However, two independent research groups, including our own, were unable to replicate these findings. In contrast, we found no Vp4 expression in SV40-infected cells and no reduction in progeny release for Vp4-deficient virus, and finally, we found that the single amino acid substitution unavoidably introduced into the overlapping Vp2/Vp3 genes during Vp4 mutagenesis reduced early steps but not virus release. Remarkably, the existence of the viroporin Vp4 still seems to be widely accepted, which presumably is preventing important research on polyomavirus release. With this perspective, we will review and comment on the most important experiments that led to the disputed announcement of the viroporin Vp4.

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The Presumed Polyomavirus Viroporin VP4 of Simian Virus 40 or Human BK Polyomavirus Is Not Required for Viral Progeny Release

Cited by 16 publications

References 54 publications

Expression of novel proteins by polyomaviruses and recent advances in the structural and functional features of agnoprotein of JC virus, BK virus, and simian virus 40

Expression of novel proteins by polyomaviruses and recent advances in the structural and functional features of agnoprotein of JC virus, BK virus, and simian virus 40

SV40 polyomavirus activates the Ras-MAPK signaling pathway for vacuolization, cell death, and virus release

Does the Evidence Support the Existence of the Simian Polyomavirus SV40 Vp4 Viroporin?

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