title: JC polyomavirus attachment, entry, and trafficking: unlocking the keys to a fatal infection.
abstract: The human JC polyomavirus (JCPyV) causes a lifelong persistent infection in the reno-urinary tract in the majority of the adult population worldwide. In healthy individuals, infection is asymptomatic, while in immunocompromised individuals, the virus can spread to the central nervous system and cause a fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). There are currently very few treatment options for this rapidly progressing and devastating disease. Understanding the basic biology of JCPyV-host cell interactions is critical for the development of therapeutic strategies to prevent or treat PML. Research in our laboratory has focused on gaining a detailed mechanistic understanding of the initial steps in the JCPyV life cycle in order to define how JCPyV selectively targets cells in the kidney and brain. JCPyV requires sialic acids to attach to host cells and initiate infection, and JCPyV demonstrates specificity for the oligosaccharide lactoseries tetrasaccharide c (LSTc) with an α2,6-linked sialic acid. Following viral attachment, JCPyV entry is facilitated by the 5-hydroxytryptamine (5-HT)2 family of serotonin receptors via clathrin-dependent endocytosis. JCPyV then undergoes retrograde transport to the endoplasmic reticulum (ER) where viral disassembly begins. A novel retrograde transport inhibitor termed Retro-2(cycl) prevents trafficking of JCPyV to the ER and inhibits both initial virus infection and infectious spread in cell culture. Understanding the molecular mechanisms by which JCPyV establishes infection will open up new avenues for the prevention or treatment of virus-induced disease.
authors: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, 02912, USA.|Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME, 04469, USA.
authors: Melissa S
authors: MS
authors: Maginnis
authors: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, 02912, USA.
authors: Christian D S
authors: CD
authors: Nelson
authors: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, 02912, USA. walter_atwood@brown.edu.
authors: Walter J
authors: WJ
authors: Atwood
mesh_terms: D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans; D007577:JC Virus / Q000472:pathogenicity*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000821:virology*; D053585:Virus Attachment; D053586:Virus Internalization
keywords: JC polyomavirus; LSTc; PML; Retro-2cycl; Serotonin receptor; Sialic acid