α-Herpesvirus glycoprotein D interaction with sensory neurons triggers formation of varicosities that serve as virus exit sites

Nick De Regge, Hans J. Nauwynck, Kristin Geenen, Claude Krummenacher, Gary H. Cohen, Roselyn J. Eisenberg, Thomas C. Mettenleiter, Herman W. Favoreel

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

α-Herpesviruses constitute closely related neurotropic viruses, including herpes simplex virus in man and pseudorabies virus (PRV) in pigs. Peripheral sensory neurons, such as trigeminal ganglion (TG) neurons, are predominant target cells for virus spread and lifelong latent infections. We report that in vitro infection of swine TG neurons with the homologous swine α-herpesvirus PRV results in the appearance of numerous synaptophysin-positive synaptic boutons (varicosities) along the axons. Nonneuronal cells that were juxtaposed to these varicosities became preferentially infected with PRV, suggesting that varicosities serve as axonal exit sites for the virus. Viral envelope glycoprotein D (gD) was found to be necessary and sufficient for the induction of varicosities. Inhibition of Cdc42 Rho GTPase and p38 mitogen- activated protein kinase signaling pathways strongly suppressed gD-induced varicosity formation. These data represent a novel aspect of the cell biology of α- herpesvirus infections of sensory neurons, demonstrating that virus attachment/entry is associated with signaling events and neuronal changes that may prepare efficient egress of progeny virus.

Original languageEnglish (US)
Pages (from-to)267-275
Number of pages9
JournalJournal of Cell Biology
Volume174
Issue number2
DOIs
StatePublished - Jul 17 2006

All Science Journal Classification (ASJC) codes

  • Cell Biology

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