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PMID: 16254350 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Journal of virology ·Vol. 79 ·No. 22 ·2005-11-00 ·Pages 14149-60

Barton ES, Lutzke ML, Rochford R, Virgin HW

Abstract

Alpha/beta interferon (IFN-alpha/beta) 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-alpha/beta also modulates the virus-host interaction during latent virus infection, we infected mice lacking the IFN-alpha/beta receptor (IFN-alpha/betaR(-/-)) and wild-type (wt; 129S2/SvPas) mice with murine gammaherpesvirus 68 (gammaHV68), a lymphotropic gamma-2-herpesvirus that establishes latent infection in B cells, macrophages, and dendritic cells. IFN-alpha/betaR(-/-) mice cleared low-dose intranasal gammaHV68 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-alpha/betaR(-/-) mice reactivated ex vivo with >40-fold- and 5-fold-enhanced efficiency, respectively, compared to wt cells. Depletion of IFN-alpha/beta from wt mice during viral latency also significantly increased viral reactivation, demonstrating an antiviral function of IFN-alpha/beta during latency. Viral reactivation efficiency was temporally regulated in both wt and IFN-alpha/betaR(-/-) mice. The mechanism of IFN-alpha/betaR action was distinct from that of IFN-gammaR, since IFN-alpha/betaR(-/-) 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-alpha/betaR(-/-) splenocytes. These data demonstrate that an IFN-alpha/beta-induced pathway regulates gammaHV68 gene expression patterns during latent viral infection in vivo and that IFN-alpha/beta plays a critical role in inhibiting viral reactivation during latency.

MeSH Terms
Animals Gammaherpesvirinae/drug effects,genetics,physiology Gene Expression Regulation, Viral/drug effects Herpesviridae Infections/immunology Interferon-alpha/pharmacology Interferon-beta/pharmacology Liver/immunology,virology Lung/immunology,virology Mice Mice, Knockout Receptors, Interferon/deficiency,genetics Spleen/immunology,virology Virus Latency/drug effects,genetics,immunology Virus Replication
Chemicals
Interferon-alpha Receptors, Interferon Interferon-beta
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Barton Erik S
Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660 S. Euclid Avenue, St. Louis, Missouri 63110, USA.
Lutzke Mary L
Rochford Rosemary
Virgin Herbert W
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.79.22.14149-14160.2005
Published
2005-11-00
Pages
14149-60
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1280204
Subset
IM
Grants
NHLBI NIH HHS · R01 HL060090 · United States
NIAID NIH HHS · AICA74730 · United States
NIAID NIH HHS · 5-T32-AI07163 · United States
NCI NIH HHS · T32 CA009547 · United States
NIA NIH HHS · AG09822 · United States
NHLBI NIH HHS · HL60090 · United States
NIAID NIH HHS · T32 AI007163 · United States
NCI NIH HHS · 5-T32-CA09547 · United States
External Links
PubMed source DOI: 10.1128/JVI.79.22.14149-14160.2005 PMC Full Text View journal details
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