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JC polyomavirus attachment, entry, and trafficking: unlocking the keys to a fatal infection

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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-2cycl 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.

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Acknowledgments

We thank all of the people that contributed to the work discussed in this review article and Gretchen Gee for critical review of the manuscript. Research in the Atwood laboratory is funded by 5P01NS065719 (W.J.A.), R01NS043097 (W.J.A.), and Ruth L. Kirschstein National Research Service Awards F32NS064870 (M.S.M.) and F32NS070687 (C.D.S.N.) from the National Institute of Neurological Disorders and Stroke. Core facilities that support our work are funded by P30GM103410 (W.J.A).

Conflict of interest

Melissa S. Maginnis declares that she has no conflict of interest. Christian D. Nelson declares that he has no conflict of interest. Walter J. Atwood declares that he has no conflict of interest.

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  1. Melissa S. Maginnis

    Present address: Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME, 04469, USA

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  1. Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, 02912, USA

    Melissa S. Maginnis, Christian D. S. Nelson & Walter J. Atwood

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  1. Melissa S. Maginnis
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Maginnis, M.S., Nelson, C.D.S. & Atwood, W.J. JC polyomavirus attachment, entry, and trafficking: unlocking the keys to a fatal infection. J. Neurovirol. 21, 601–613 (2015). https://doi.org/10.1007/s13365-014-0272-4

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