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Journal of Virology, April 2007, p. 3704-3713, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02626-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Susceptibility of CCR5-Deficient Mice to Genital Herpes Simplex Virus Type 2 Is Linked to NK Cell Mobilization{triangledown}

Manoj Thapa,1 William A. Kuziel,2 and Daniel J. J. Carr1,3*

Departments of Microbiology and Immunology,1 Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104,3 Protein Design Labs, Inc., Fremont, California 945552

Received 28 November 2006/ Accepted 23 January 2007

Following genital herpes simplex virus type 2 (HSV-2) exposure, NK cells and T cells are mobilized to sites of infection to control viral replication and spread. The present investigation sought to determine the role of the chemokine receptor CCR5 in this process. Mice deficient in CCR5 (CCR5–/–) displayed a significant reduction in cumulative survival following infection in comparison to wild-type, HSV-2-infected controls. Associated with decreased resistance to viral infection, CCR5–/– mice yielded significantly more virus and expressed higher levels of tumor necrosis factor alpha, CXCL1, CCL2, CCL3, and CCL5 in the vagina, spinal cord, and/or brain stem than did wild-type mice. Whereas there was no difference in absolute number of leukocytes (CD45high), CD4 T cells, or CD8 T cells residing in the draining lymph nodes, spleen, spinal cord, or brain stem comparing HSV-2-infected wild-type to CCR5–/– mice prior to or after infection, there were significantly more NK cells (NK1.1+ CD3–) residing in the brain stem and spleen of infected wild-type mice. Functionally, NK activity from cells isolated from the brain stem of HSV-2-infected wild-type mice was greater than that from HSV-2-infected CCR5–/– mice. In addition, antibody-mediated depletion of NK cells resulted in an increase in HSV-2 levels in the vaginal, spinal cord, and brain stem tissue of wild-type but not CCR5–/– mice. Collectively, the absence of CCR5 expression significantly impacts the ability of the host to control genital HSV-2 infection, inflammation, and spread associated with a specific reduction in NK cell expansion, infiltration, and activity in the nervous system.

* Corresponding author. Mailing address: Department of Ophthalmology, DMEI #415, The 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 31 January 2007.

Journal of Virology, April 2007, p. 3704-3713, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02626-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Thapa, M., Carr, D. J. J. (2009). CXCR3 Deficiency Increases Susceptibility to Genital Herpes Simplex Virus Type 2 Infection: Uncoupling of CD8+ T-Cell Effector Function but Not Migration. J. Virol. 83: 9486-9501 [Abstract] [Full Text]  
  • Kassim, S. H., Rajasagi, N. K., Ritz, B. W., Pruett, S. B., Gardner, E. M., Chervenak, R., Jennings, S. R. (2009). Dendritic Cells Are Required for Optimal Activation of Natural Killer Functions following Primary Infection with Herpes Simplex Virus Type 1. J. Virol. 83: 3175-3186 [Abstract] [Full Text]  
  • Thapa, M., Carr, D. J. J. (2008). Herpes Simplex Virus Type 2-Induced Mortality following Genital Infection Is Blocked by Anti-Tumor Necrosis Factor Alpha Antibody in CXCL10-Deficient Mice. J. Virol. 82: 10295-10301 [Abstract] [Full Text]  
  • Jia, T., Serbina, N. V., Brandl, K., Zhong, M. X., Leiner, I. M., Charo, I. F., Pamer, E. G. (2008). Additive Roles for MCP-1 and MCP-3 in CCR2-Mediated Recruitment of Inflammatory Monocytes during Listeria monocytogenes Infection. J. Immunol. 180: 6846-6853 [Abstract] [Full Text]  
  • Thapa, M., Welner, R. S., Pelayo, R., Carr, D. J. J. (2008). CXCL9 and CXCL10 Expression Are Critical for Control of Genital Herpes Simplex Virus Type 2 Infection through Mobilization of HSV-Specific CTL and NK Cells to the Nervous System. J. Immunol. 180: 1098-1106 [Abstract] [Full Text]  


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