Interferon regulatory factor 3-dependent pathways are critical for control of herpes simplex virus type 1 central nervous system infection

Vineet Menachery, Tracy Jo Pasieka, David A. Leib

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The initiation of the immune response at the cellular level relies on specific recognition molecules to rapidly signal viral infection via interferon (IFN) regulatory factor 3 (IRF-3)-dependent pathways. The absence of IRF-3 would be expected to render such pathways inoperative and thereby significantly affect viral infection. Unexpectedly, a previous study found no significant change in herpes simplex virus (HSV) pathogenesis in IRF-3-/- mice following intravenous HSV type 1 (HSV-1) challenge (K. Honda, H. Yanai, H. Negishi, M. Asagiri, M. Sato, T. Mizutani, N. Shimada, Y. Ohba, A. Takaoka, N. Yoshida, and T. Taniguchi, Nature 434:772-777, 2005). In contrast, the present study demonstrated that IRF-3-/- mice are significantly more susceptible to HSV infection via the corneal and intracranial routes. Following corneal infection with 2 × 106 PFU of HSV-1 strain McKrae, 50% of wild-type mice survived, compared to 10% of IRF-3-deficient mice. Significantly increased viral replication and inflammatory cytokine production were observed in brain tissues of IRF-3-/- mice compared to control mice, with a concomitant deficit in production of both IFN-β and IFN-α. These data demonstrate a critical role for IRF-3 in control of central nervous system infection following HSV-1 challenge. Furthermore, this work underscores the necessity to evaluate multiple routes of infection and animal models in order to fully determine the role of host resistance factors in pathogenesis.

Original languageEnglish (US)
Pages (from-to)9685-9694
Number of pages10
JournalJournal of Virology
Volume84
Issue number19
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

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Interferon Regulatory Factor-3
Human herpesvirus 1
Central Nervous System Infections
Critical Pathways
Human Herpesvirus 1
central nervous system
mice
infection
Virus Diseases
herpes simplex
interferons
Simplexvirus
Interferons
pathogenesis
viruses
virus replication
R Factors
Infection
interferon regulatory factor-3
Cellular Immunity

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Medicine(all)

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Interferon regulatory factor 3-dependent pathways are critical for control of herpes simplex virus type 1 central nervous system infection. / Menachery, Vineet; Pasieka, Tracy Jo; Leib, David A.

In: Journal of Virology, Vol. 84, No. 19, 01.01.2010, p. 9685-9694.

Research output: Contribution to journalArticle

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