Suppression of proinflammatory cytokine expression by herpes simplex virus type 1

Trine H. Mogensen, Jesper Melchjorsen, Lene Malmgaard, Antonella Casola, Søren R. Paludan

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Viral immune evasion strategies are important for establishment and maintenance of infections. Many viruses are in possession of mechanisms to counteract the antiviral response raised by the infected host. Here we show that a herpes simplex virus type 1 (HSV-1) mutant lacking functional viral protein 16 (VP16)-a tegument protein promoting viral gene expression-induced significantly higher levels of proinflammatory cytokines than wild-type HSV-1. This was observed in several cell lines and primary murine macrophages, as well as in peritoneal cells harvested from mice infected in vivo. The enhanced ability to stimulate cytokine expression in the absence of VP16 was not mediated directly by VP16 but was dependent on the viral immediate-early genes for infected cell protein 4 (ICP4) and ICP27, which are expressed in a VP16-dependent manner during primary HSV infection. The virus appeared to target cellular factors other than interferon-induced double-stranded RNA-activated protein kinase R (PKR), since the virus mutants remained stronger inducers of cytokines in cells stably expressing a dominant-negative mutant form of PKR. Finally, mRNA stability assay revealed a significantly longer half-life for interleukin-6 mRNA after infection with the VP16 mutant than after infection with the wild-type virus. Thus, HSV is able to suppress expression of proinflammatory cytokines by decreasing the stability of mRNAs, thereby potentially impeding the antiviral host response to infection.

Original languageEnglish (US)
Pages (from-to)5883-5890
Number of pages8
JournalJournal of Virology
Volume78
Issue number11
DOIs
StatePublished - Jun 2004

Fingerprint

Human herpesvirus 1
viral proteins
Human Herpesvirus 1
Viral Proteins
cytokines
Cytokines
viruses
mutants
infection
Viruses
Infection
protein kinases
RNA Stability
Antiviral Agents
immune evasion
eIF-2 Kinase
double-stranded RNA
mice
Immune Evasion
cells

ASJC Scopus subject areas

  • Immunology

Cite this

Suppression of proinflammatory cytokine expression by herpes simplex virus type 1. / Mogensen, Trine H.; Melchjorsen, Jesper; Malmgaard, Lene; Casola, Antonella; Paludan, Søren R.

In: Journal of Virology, Vol. 78, No. 11, 06.2004, p. 5883-5890.

Research output: Contribution to journalArticle

Mogensen, Trine H. ; Melchjorsen, Jesper ; Malmgaard, Lene ; Casola, Antonella ; Paludan, Søren R. / Suppression of proinflammatory cytokine expression by herpes simplex virus type 1. In: Journal of Virology. 2004 ; Vol. 78, No. 11. pp. 5883-5890.
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