Control of herpes simplex virus replication is mediated through an interferon regulatory factor 3-dependent pathway

Vineet Menachery, David A. Leib

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The type I interferon (IFN) cascade is critical in controlling viral replication and pathogenesis. Recognition pathways triggered by viral infection rapidly induce the type I IFN cascade, often in an IFN regulatory factor 3 (IRF-3)-dependent fashion. This dependence predicts that loss of IRF-3 would render early recognition pathways inoperative and thereby impact virus replication, but this has not been observed previously with herpes simplex virus type 1 (HSV-1) in vitro. In this study, HSV-1-infected IRF-3-/- bone marrow-derived dendritic cells (BMDCs) and macrophages supported increased HSV replication compared to control cells. In addition, IRF-3-deficient BMDCs exhibited delayed type I IFN synthesis compared to control cells. However, while IFN pretreatment of IRF-3-/- BMDCs resulted in reduced virus titers, a far greater reduction was seen after IFN treatment of wild-type cells. This suggests that even in the presence of exogenously supplied IFN, IRF-3 -/- BMDCs are inherently defective in the control of HSV-1 replication. Together, these results demonstrate a critical role for IRF-3-mediated pathways in controlling HSV-1 replication in cells of the murine immune system.

Original languageEnglish (US)
Pages (from-to)12399-12406
Number of pages8
JournalJournal of Virology
Volume83
Issue number23
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

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Interferon Regulatory Factor-3
herpes simplex
interferons
Simplexvirus
Virus Replication
virus replication
Human herpesvirus 1
dendritic cells
bone marrow
Human Herpesvirus 1
Interferon Type I
Dendritic Cells
Bone Marrow
cells
Interferons
viral load
immune system
interferon regulatory factor-3
macrophages
Virus Diseases

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Control of herpes simplex virus replication is mediated through an interferon regulatory factor 3-dependent pathway. / Menachery, Vineet; Leib, David A.

In: Journal of Virology, Vol. 83, No. 23, 01.12.2009, p. 12399-12406.

Research output: Contribution to journalArticle

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