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Journal of Virology, October 2005, p. 12658-12666, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12658-12666.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Varicella-Zoster Virus Activates Inflammatory Cytokines in Human Monocytes and Macrophages via Toll-Like Receptor 2

Jennifer P. Wang,1* Evelyn A. Kurt-Jones,1 Ok S. Shin,1 Michael D. Manchak,2 Myron J. Levin,2 and Robert W. Finberg1

Department of Medicine, University of Massachusetts Medical Center, 364 Plantation Street, Worcester, Massachusetts 01605,1 Section of Pediatric Infectious Diseases, School of Medicine, University of Colorado, Denver, Colorado 802622

Received 22 March 2005/ Accepted 27 July 2005

The pattern recognition receptor Toll-like receptor 2 (TLR2) has been implicated in the response to several human viruses, including herpes simplex viruses (types 1 and 2) and cytomegalovirus. We demonstrated that varicella-zoster virus (VZV) activates inflammatory cytokine responses via TLR2. VZV specifically induced interleukin-6 (IL-6) in human monocytes via TLR2-dependent activation of NF-{kappa}B, and small interfering RNA designed to suppress TLR2 mRNA reduced the IL-6 response to VZV in human monocyte-derived macrophages. Unlike other herpesviruses, the cytokine response to VZV was species specific. VZV did not induce cytokines in murine embryonic fibroblasts or in a mouse cell line, although VZV did activate NF-{kappa}B in a human cell line expressing a murine TLR2 construct. Together, these results suggest that TLR2 may play a role in the inflammatory response to VZV infection.

* Corresponding author. Mailing address: LRB 219, 364 Plantation Street, Worcester, MA 01605. Phone: (508) 856-8414. Fax: (508) 856-6176. E-mail: jennifer.wang{at}umassmed.edu.

Journal of Virology, October 2005, p. 12658-12666, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12658-12666.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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