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

Abstract

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.

BK polyomavirus evades innate immune sensing by disrupting the mitochondrial network and membrane potential and by promoting mitophagy

“…Our results also shed new light on previous reports on BKPyV agnoprotein and the closely related JCPyV and SV40 homologues (Gerits and Moens, 2012;Saribas et al, 2018): These include facilitating polyomavirus replication (Ng et al, 1985), increasing viral late phase production (Carswell et al, 1986) and plaques size (Hou-Jong et al, 1987), acting as egress factor (Panou et al, 2018) or as viroporin (Suzuki et al, 2010). We demonstrate that mitochondrial fragmentation occurs not only for BKPyV strains carrying an archetype NCCR, but also for the human JCPyV or the monkey SV40 supporting the view that this dramatic agnoprotein-mediated function is evolutionary conserved across different species, cell types and hosts.…”

Association Between Simian Virus 40 and Human Tumors

“…VP 4 seems to facilitate the lytic release of the SV40 virions (24), but a recent study demonstrated that VP4 is not required for this process (25). The agnoprotein controls the perinuclear localization of VP 1 during virion formation, which then triggers virion assembly (26). In total, SV40 translates for nine proteins.…”

A Comprehensive Proteomics Analysis of the JC Virus (JCV) Large and Small Tumor Antigen Interacting Proteins: Large T Primarily Targets the Host Protein Complexes with V-ATPase and Ubiquitin Ligase Activities While Small t Mostly Associates with Those Having Phosphatase and Chromatin-Remodeling Functions

“…The early regulatory proteins of JCV tumor antigens, LT-Ag and Sm t-Ag, are produced by the alternative splicing of the viral early transcripts [ 13 ] ( Figure 3 A). Both play critical roles in the viral life cycle [ 48 , 72 , 92 , 143 , 144 , 145 ].…”

“…The discovery of additional human polyomaviruses has been recently facilitated due to availability of the new technologies, including the rolling circle amplification and digital transcriptome subtraction. The current number of human polyomavirus has now risen to 14 [ 13 , 14 ]. Note that not every isolated human polyomavirus was proven to be associated with any particular human disease.…”