Alpha/beta interferons regulate murine gammaherpesvirus latent gene expression and reactivation from latency

Erik S. Barton, Mary L. Lutzke, Rosemary Rochford, Herbert W. Virgin IV

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Alpha/beta interferon (IFN-α/β) protects the host from virus infection by inhibition of lytic virus replication in infected cells and modulation of the antiviral cell-mediated immune response. To determine whether IFN-α/β also modulates the virus-host interaction during latent virus infection, we infected mice lacking the IFN-α/β receptor (IFN-α/βR-/-) and wild-type (wt; 12982/SvPas) mice with murine gammaherpesvirus 68 (γHV68), a lymphotropic gamma-2-herpesvirus that establishes latent infection in B cells, macrophages, and dendritic cells. IFN-α/βR-/- mice cleared low-dose intranasal γHV68 infection with wt kinetics and harbored essentially wt frequencies of latently infected cells in both peritoneum and spleen by 28 days postinfection. However, latent virus in peritoneal cells and splenocytes from IFN-α/βR -/- mice reactivated ex vivo with >40-fold- and 5-fold-enhanced efficiency, respectively, compared to wt cells. Depletion of IFN-α/β from wt mice during viral latency also significantly increased viral reactivation, demonstrating an antiviral function of IFN-α/β during latency. Viral reactivation efficiency was temporally regulated in both wt and IFN-α/βR-/- mice. The mechanism of IFN-α/βR action was distinct from that of IFN-γR, since IFN-α/βR -/- mice did not display persistent virus replication in vivo. Analysis of viral latent gene expression in vivo demonstrated specific upregulation of the latency-associated gene M2, which is required for efficient reactivation From latency, in IFN-α/βR-/- splenocytes. These data demonstrate that an IFN-α/β-induced pathway regulates γHV68 gene expression patterns daring latent viral infection in vivo and that IFN-α/β plays a critical role in inhibiting viral reactivation during latency.

Original languageEnglish
Pages (from-to)14149-14160
Number of pages12
JournalJournal of virology
Volume79
Issue number22
DOIs
StatePublished - Nov 1 2005

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