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 Scopus citations

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

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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