Journal article
Herpes simplex virus US3 tegument protein inhibits Toll-like receptor 2 signaling at or before TRAF6 ubiquitination
Virology (New York, N.Y.), Vol.439(2), pp.65-73
05/10/2013
DOI: 10.1016/j.virol.2013.01.026
PMCID: PMC3810314
PMID: 23478027
Abstract
Herpes simplex virus (HSV) has evolved multiple strategies to modulate host immune responses. In a screen of HSV open reading frames to identify additional HSV-encoded proteins that affect NF-κB signaling, we identified the viral US3 tegument protein as an inhibitor of NF-κB signaling. We found that the US3 protein is required for inhibition of TLR2 signaling induced by viral infection and that this inhibition occurs at very early times post-infection. Expression of US3 in transfected cells inhibits TLR2 signaling induced by Zymosan, and this inhibition occurs at or downstream of MyD88 and upstream of p65. Polyubiquitination of TRAF6 is critical for its function in TLR2 signaling. Using US3-null and US3 kinase-defective mutant viruses, we demonstrate that HSV US3 reduces TRAF6 polyubiquitination and that the kinase activity of US3 is necessary for this effect. Therefore, US3 is necessary and sufficient for inhibiting TLR2 signaling at or before the stage of TRAF6 ubiquitination.
► HSV tegument protein US3 inhibits NF-κB signaling downstream of TLR2 at early times post-infection. ► US3 inhibits NF-κB signaling downstream of MyD88 but at or before TRAF6 ubiquitination. ► The kinase activity of US3 is necessary for this effect.
Details
- Title: Subtitle
- Herpes simplex virus US3 tegument protein inhibits Toll-like receptor 2 signaling at or before TRAF6 ubiquitination
- Creators
- Jayita Sen - Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USAXueqiao Liu - Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USARichard Roller - Department of Microbiology and Immunology, University of Iowa Medical School, Iowa City, IA, USADavid M Knipe - Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA
- Resource Type
- Journal article
- Publication Details
- Virology (New York, N.Y.), Vol.439(2), pp.65-73
- DOI
- 10.1016/j.virol.2013.01.026
- PMID
- 23478027
- PMCID
- PMC3810314
- NLM abbreviation
- Virology
- ISSN
- 0042-6822
- eISSN
- 1096-0341
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: AI39576, AI057552
- Language
- English
- Date published
- 05/10/2013
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984001161502771
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