Herpes simplex virus downregulates secretory leukocyte protease inhibitor

A novel immune evasion mechanism

Esra Fakioglu, Sarah S. Wilson, Pedro M M Mesquita, Ehsan Hazrati, Natalia V. Cheshenko, John A. Blaho, Betsy Herold

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Secretory leukocyte protease inhibitor (SLPI), an anti-inflammatory mediator of mucosal immunity, inhibits human immunodeficiency virus (HIV) and herpes simplex virus (HSV) in cell culture. Epidemiological studies demonstrate that higher concentrations of SLPI in mucosal secretions are associated with a reduced risk of HIV transmission. The current studies were designed to test the hypothesis that HSV triggers a loss of SLPI to evade innate immunity and that this response may contribute to the increased risk of HIV infection in the setting of HSV infection. Exposure of human cervical epithelial cells to HSV-1 or HSV-2, but not HIV or vesicular stomatitis virus, triggered a significant and sustained reduction in SLPI levels. The reduction persisted when cells were infected in the presence of acyclovir but not following infection with UV-inactivated virus, indicating that viral gene expression, but not replication, is required. Reverse transcriptase PCR studies demonstrated that the loss of SLPI is mediated by downregulation of gene expression. SLPI downregulation was associated with activation of NF-κB signaling pathways and upregulation of proinflammatory cytokines, consistent with the known inhibitor effects of SLPI on NF-κB pathways. The downregulation mapped to viral early-gene expression, as variants impaired in expression of the ICP4 or ICP0 immediate-early gene failed to downregulate SLPI or activate NF-κB. Together, these results identify a novel role for HSV immediate-early-gene expression in regulating mucosal immune responses.

Original languageEnglish (US)
Pages (from-to)9337-9344
Number of pages8
JournalJournal of Virology
Volume82
Issue number19
DOIs
StatePublished - Oct 2008

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Secretory Leukocyte Peptidase Inhibitor
immune evasion
Immune Evasion
herpes simplex
Simplexvirus
proteinase inhibitors
leukocytes
Down-Regulation
viruses
Human immunodeficiency virus
HIV
Gene Expression
mucosal immunity
gene expression
Mucosal Immunity
Immediate-Early Genes
Viral Genes
Virus Diseases
Human herpesvirus 2
Viruses

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Herpes simplex virus downregulates secretory leukocyte protease inhibitor : A novel immune evasion mechanism. / Fakioglu, Esra; Wilson, Sarah S.; Mesquita, Pedro M M; Hazrati, Ehsan; Cheshenko, Natalia V.; Blaho, John A.; Herold, Betsy.

In: Journal of Virology, Vol. 82, No. 19, 10.2008, p. 9337-9344.

Research output: Contribution to journalArticle

Fakioglu, Esra ; Wilson, Sarah S. ; Mesquita, Pedro M M ; Hazrati, Ehsan ; Cheshenko, Natalia V. ; Blaho, John A. ; Herold, Betsy. / Herpes simplex virus downregulates secretory leukocyte protease inhibitor : A novel immune evasion mechanism. In: Journal of Virology. 2008 ; Vol. 82, No. 19. pp. 9337-9344.
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