Short interfering RNA-mediated inhibition of herpes simplex virus type 1 gene expression and function during infection of human keratinocytes

Prakash K. Bhuyan, Katalin Karikò, John Capodici, John Lubinski, Lauren M. Hook, Harvey M. Friedman, Drew Weissman

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

RNA interference (RNAi) is an antiviral mechanism that is activated when double-stranded RNA is cleaved into fragments, called short interfering RNA (siRNA), that prime an inducible gene silencing enzyme complex. We applied RNAi against a herpes simplex virus type 1 (HSV-1) gene, glycoprotein E, which mediates cell-to-cell spread and immune evasion. In an in vitro model of infection, human keratinocytes were transfected with siRNA specific for glycoprotein E and then infected with wild-type HSV-1. RNAi-mediated gene silencing reproduced the small plaque phenotype of a gE-deletion mutant virus. The specificity of gene targeting was demonstrated by flow cytometry and Northern blot analyses. Exogenous siRNA can suppress HSV-1 glycoprotein E expression and function during active infection in vitro through RNAi. This work establishes RNAi as a genetic tool for the study of HSV and provides a foundation for development of RNAi as a novel antiviral therapy.

Original languageEnglish (US)
Pages (from-to)10276-10281
Number of pages6
JournalJournal of Virology
Volume78
Issue number19
DOIs
StatePublished - Oct 2004
Externally publishedYes

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Human herpesvirus 1
keratinocytes
Human Herpesvirus 1
small interfering RNA
RNA Interference
RNA interference
Keratinocytes
Small Interfering RNA
Gene Expression
gene expression
Infection
infection
glycoproteins
Gene Silencing
gene silencing
Antiviral Agents
immune evasion
Immune Evasion
Double-Stranded RNA
Gene Targeting

ASJC Scopus subject areas

  • Immunology

Cite this

Short interfering RNA-mediated inhibition of herpes simplex virus type 1 gene expression and function during infection of human keratinocytes. / Bhuyan, Prakash K.; Karikò, Katalin; Capodici, John; Lubinski, John; Hook, Lauren M.; Friedman, Harvey M.; Weissman, Drew.

In: Journal of Virology, Vol. 78, No. 19, 10.2004, p. 10276-10281.

Research output: Contribution to journalArticle

Bhuyan, Prakash K. ; Karikò, Katalin ; Capodici, John ; Lubinski, John ; Hook, Lauren M. ; Friedman, Harvey M. ; Weissman, Drew. / Short interfering RNA-mediated inhibition of herpes simplex virus type 1 gene expression and function during infection of human keratinocytes. In: Journal of Virology. 2004 ; Vol. 78, No. 19. pp. 10276-10281.
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