An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection

Deborah Palliser, Dipanjan Chowdhury, Qing Yin Wang, Sandra J. Lee, Roderick T. Bronson, David M. Knipe, Judy Lieberman

Research output: Contribution to journalArticle

328 Citations (Scopus)

Abstract

Herpes simplex virus 2 (HSV-2) infection causes significant morbidity 1 and is an important cofactor for the transmission of HIV infection2. A microbicide to prevent sexual transmission of HSV-2 would contribute substantially to controlling the spread of HIV and other infections3,4. Because RNA interference (RNAi) provides effective antiviral defence in plants and other organisms, several studies have focused on harnessing RNAi to inhibit viral infection5. Here we show that vaginal instillation of small interfering RNAs (siRNAs) targeting HSV-2 protects mice from lethal infection. siRNAs mixed with lipid are efficiently taken up by epithelial and lamina propria cells and silence gene expression in the mouse vagina and ectocervix for at least nine days. Intravaginal application of siRNAs targeting the HSV-2 UL27and UL29 genes (which encode an envelope glycoprotein and a DNA binding protein6, respectively) was well tolerated, did not induce interferon-responsive genes or cause inflammation, and protected mice when administered before and/or after lethal HSV-2 challenge. These results suggest that siRNAs are attractive candidates for the active component of a microbicide designed to prevent viral infection or transmission.

Original languageEnglish (US)
Pages (from-to)89-94
Number of pages6
JournalNature
Volume439
Issue number7072
DOIs
StatePublished - Jan 5 2006
Externally publishedYes

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Human Herpesvirus 2
Virus Diseases
Anti-Infective Agents
Small Interfering RNA
RNA Interference
Intravaginal Administration
HIV
Infectious Disease Transmission
Vagina
Interferons
Genes
Antiviral Agents
Glycoproteins
Mucous Membrane
Inflammation
Morbidity
Lipids
Gene Expression
DNA
Infection

ASJC Scopus subject areas

  • General

Cite this

Palliser, D., Chowdhury, D., Wang, Q. Y., Lee, S. J., Bronson, R. T., Knipe, D. M., & Lieberman, J. (2006). An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. Nature, 439(7072), 89-94. https://doi.org/10.1038/nature04263

An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. / Palliser, Deborah; Chowdhury, Dipanjan; Wang, Qing Yin; Lee, Sandra J.; Bronson, Roderick T.; Knipe, David M.; Lieberman, Judy.

In: Nature, Vol. 439, No. 7072, 05.01.2006, p. 89-94.

Research output: Contribution to journalArticle

Palliser, D, Chowdhury, D, Wang, QY, Lee, SJ, Bronson, RT, Knipe, DM & Lieberman, J 2006, 'An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection', Nature, vol. 439, no. 7072, pp. 89-94. https://doi.org/10.1038/nature04263
Palliser D, Chowdhury D, Wang QY, Lee SJ, Bronson RT, Knipe DM et al. An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. Nature. 2006 Jan 5;439(7072):89-94. https://doi.org/10.1038/nature04263
Palliser, Deborah ; Chowdhury, Dipanjan ; Wang, Qing Yin ; Lee, Sandra J. ; Bronson, Roderick T. ; Knipe, David M. ; Lieberman, Judy. / An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. In: Nature. 2006 ; Vol. 439, No. 7072. pp. 89-94.
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