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Journal of Virology, October 2008, p. 10295-10301, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.00931-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Herpes Simplex Virus Type 2-Induced Mortality following Genital Infection Is Blocked by Anti-Tumor Necrosis Factor Alpha Antibody in CXCL10-Deficient Mice{triangledown}

Manoj Thapa1 and Daniel J. J. Carr1,2*

Departments of Microbiology, Immunology,1 Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 731042

Received 5 May 2008/ Accepted 29 July 2008

The role of tumor necrosis factor alpha (TNF-{alpha}) was evaluated for CXCL10-deficient (CXCL10–/–) mice which succumbed to genital herpes simplex virus type 2 (HSV-2) infection and possessed elevated levels of virus and TNF-{alpha} but not other cytokines in the central nervous system (CNS) and vaginal tissue within the first 7 days following virus exposure. Anti-TNF-{alpha} but not control antibody treatment offsets the elevated mortality rate of CXCL10–/– mice, despite increased CNS viral titers. In addition, TNF-{alpha} neutralization suppressed recruitment of leukocyte subpopulations into the CNS, which is associated with reduced CCL2 and CXCL9 expression. Collectively, the results implicate TNF-{alpha} as the principal mediator of mortality in response to genital HSV-2 infection.


* Corresponding author. Mailing address: Department of Ophthalmology, DMEI #415, University of Oklahoma Health Sciences Center, 608 Stanton L Young Blvd., Oklahoma City, OK 73104. Phone: (405) 271-8784. Fax: (405) 271-8781. E-mail: dan-carr{at}ouhsc.edu

{triangledown} Published ahead of print on 6 August 2008.


Journal of Virology, October 2008, p. 10295-10301, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.00931-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.







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