Colleen L Mayberry1, Christian D S Nelson2, Melissa S Maginnis1,3. 1. Department of Molecular and Biomedical Sciences, The University of Maine, Orono, ME, USA. 2. Biological Sciences Department, SUNY Cortland, Cortland, NY, USA. 3. Graduate School in Biomedical Sciences and Engineering, The University of Maine, Orono, ME, USA.
Abstract
PURPOSE OF REVIEW: JC polyomavirus (JCPyV) is a significant human pathogen that causes an asymptomatic infection in the kidney in the majority of the population. In immunosuppressed individuals, the virus can become reactivated and spread to the brain, causing the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). There are currently limited treatment options for this fatal disease. Attachment to receptors and entry into host cells are the initiating events in JCPyV infection and therefore an attractive target for therapeutics to prevent or treat PML. This review provides the current understanding of JCPyV attachment and entry events and the potential therapeutics to target these areas. RECENT FINDINGS: JCPyV attachment and entry to host cells is mediated by α2,6-linked lactoseries tetrasaccharide c (LSTc) and 5-hydroxytryptamine receptors (5-HT2Rs), respectively, and subsequent trafficking to the endoplasmic reticulum is required for infection. Recently, vaccines, monoclonal antibodies, and small molecules have shown promise as anti-viral and PML therapies. SUMMARY: This review summarizes our current understanding of JCPyV attachment, entry, and trafficking and the development of potential PML therapeutics that inhibit these critical steps in JCPyV infection.
PURPOSE OF REVIEW: JC polyomavirus (JCPyV) is a significant human pathogen that causes an asymptomatic infection in the kidney in the majority of the population. In immunosuppressed individuals, the virus can become reactivated and spread to the brain, causing the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). There are currently limited treatment options for this fatal disease. Attachment to receptors and entry into host cells are the initiating events in JCPyV infection and therefore an attractive target for therapeutics to prevent or treat PML. This review provides the current understanding of JCPyV attachment and entry events and the potential therapeutics to target these areas. RECENT FINDINGS:JCPyV attachment and entry to host cells is mediated by α2,6-linked lactoseriestetrasaccharide c (LSTc) and 5-hydroxytryptamine receptors (5-HT2Rs), respectively, and subsequent trafficking to the endoplasmic reticulum is required for infection. Recently, vaccines, monoclonal antibodies, and small molecules have shown promise as anti-viral and PML therapies. SUMMARY: This review summarizes our current understanding of JCPyV attachment, entry, and trafficking and the development of potential PML therapeutics that inhibit these critical steps in JCPyV infection.
Authors: Yukako Fujinaga; Anne A Wolf; Chiara Rodighiero; Heidi Wheeler; Billy Tsai; Larry Allen; Michael G Jobling; Tom Rapoport; Randall K Holmes; Wayne I Lencer Journal: Mol Biol Cell Date: 2003-09-17 Impact factor: 4.138