Viral proteomics: A promising approach for understanding JC virus tropism

Abstract

The human polyomavirus JC virus (JCV) is responsible for the CNS demyelination observed in cases of progressive multifocal leukoencephalopathy. The JCV regulatory region (promoter) is a hypervariable, noncoding, nucleotide sequence positioned between the early and late protein-coding regions in the viral genome. Selective binding of cellular transcription factors to this promoter region participates in the control of viral tropism. Hence, further study of these proteins might provide new insights into JCV tropism and associated pathogenesis. This review gives an overview of viral proteomics - the study of all proteins expressed from the viral gene transcripts, and all the cellular proteins that play a role in JCV tropism. It also describes a new biochemical approach for studying relevant JCV promoter-binding proteins, which is an anchored-JCV transcriptional promoter (ATP) assay. An ATP assay utilizes the product of PCR-amplified JCV promoter sequences coupled with Sepharose beads in order to capture and isolate cellular nuclear proteins with specific promoter-binding affinity for analysis. Proteins that bind to JCV-ATPs can be eluted and subjected to proteomic analysis. Insights from this approach may improve the understanding of viral and cellular parameters that control JCV tropism.

Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients

“…The viral genome codes for six genes: Large and small T antigen, capsid genes VP1, VP2 and VP3, agnoprotein and the regulatory region (RR), which can be classified as the archetype or rearranged according to their structural features 5 . The genetic structure of RR directly affects viral transcription and replication by change the level of DNA/protein and cofactors binding sites, thus leading to distinct cellular tropism 6 . The urinary shedding of JCV with archetype structure is frequent among healthy and immunocompromised individuals 7,8,9,10 , but rearranged forms with deletions, insertions and duplications are usually found in viruses from blood and brain of patients with PML 11,12 .…”

Early and late promoters of BK polyomavirus, Merkel cell polyomavirus, Trichodysplasia spinulosa-associated polyomavirus and human polyomavirus 12 are among the strongest of all known human polyomaviruses in 10 different cell lines

“…Although BKPyV is considered a nephrotropic virus, viral proteins and nucleic acids have been detected in several other tissues and organs including bladder, blood, bone, brain and central nervous system (CNS), male and female genitals, heart, lung, liver, skin, salivary glands and spleen (Burger-Calderon et al, 2014;Rekvig & Moens, 2002). Brain and CNS, peripheral blood cells, kidney, lungs, lymphoid organs, tonsils and gastrointestinal tract have been shown to harbour JCPyV (Boothpur & Brennan, 2010;Dörries et al, 2003;Ravichandran & Major, 2006). KIPyV and WUPyV were originally discovered in respiratory tract secretions, but DNA of these viruses has also been detected in blood, lymphoid tissue, stool, tonsil tissue and brain (Barzon et al, 2009a;Moens et al, 2010;Sharp et al, 2009).…”

White Spot Syndrome Virus Proteins and Differentially Expressed Host Proteins Identified in Shrimp Epithelium by Shotgun Proteomics and Cleavable Isotope-Coded Affinity Tag

“…Proteomics has been demonstrated to be an important platform technology and has contributed to our understanding of virus-host interaction (4,37). Shotgun two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) is a promising approach for high-throughput identification of proteins (21,48).…”