The human alpha defensin HD5 neutralizes JC polyomavirus infection by reducing endoplasmic reticulum traffic and stabilizing the viral capsid

Stephen R. Zins, Christian D S Nelson, Melissa S. Maginnis, Rahul Banerjee, Bethany A. O'Hara, Walter J. Atwood

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Progressive multifocal leukoencephalopathy (PML) is a fatal disease with limited treatment options, both clinically and in the research pipeline. Potential therapies would target and neutralize its etiologic agent, JC polyomavirus (JCPyV). The innate immune response to JCPyV infection has not been studied, and little is known about the initial host response to polyomavirus infection. This study examined the ability of a human alpha defensin, HD5, to neutralize JCPyV infection in human fetal glial cells. We show that HD5, by binding to the virion, blocks infection. The JCPyV-HD5 complexes bind to and enter host cells but are reduced in their ability to reach the endoplasmic reticulum (ER), where virions are normally uncoated. Furthermore, HD5 binding to the virion stabilizes the capsid and prevents genome release. Our results show that HD5 neutralizes JCPyV infection at an early postentry step in the viral life cycle by stabilizing the viral capsid and disrupting JCPyV trafficking. This study provides a naturally occurring platform for developing antivirals to treat PML and also expands on the known capabilities of human defensins.

Original languageEnglish (US)
Pages (from-to)948-960
Number of pages13
JournalJournal of Virology
Volume88
Issue number2
DOIs
StatePublished - Jan 2014

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JC polyomavirus
Polyomavirus Infections
alpha-Defensins
JC Virus
capsid
Capsid
traffic
Endoplasmic Reticulum
endoplasmic reticulum
virion
infection
Virion
Progressive Multifocal Leukoencephalopathy
Polyomavirus
Defensins
neuroglia
Life Cycle Stages
Innate Immunity
Neuroglia
Antiviral Agents

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

The human alpha defensin HD5 neutralizes JC polyomavirus infection by reducing endoplasmic reticulum traffic and stabilizing the viral capsid. / Zins, Stephen R.; Nelson, Christian D S; Maginnis, Melissa S.; Banerjee, Rahul; O'Hara, Bethany A.; Atwood, Walter J.

In: Journal of Virology, Vol. 88, No. 2, 01.2014, p. 948-960.

Research output: Contribution to journalArticle

Zins, Stephen R. ; Nelson, Christian D S ; Maginnis, Melissa S. ; Banerjee, Rahul ; O'Hara, Bethany A. ; Atwood, Walter J. / The human alpha defensin HD5 neutralizes JC polyomavirus infection by reducing endoplasmic reticulum traffic and stabilizing the viral capsid. In: Journal of Virology. 2014 ; Vol. 88, No. 2. pp. 948-960.
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