This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ank, N.
Right arrow Articles by Paludan, S. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ank, N.
Right arrow Articles by Paludan, S. R.

 Previous Article  |  Next Article 

Journal of Virology, August 2005, p. 9831-9841, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9831-9841.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Age-Dependent Role for CCR5 in Antiviral Host Defense against Herpes Simplex Virus Type 2

Nina Ank, Klavs Petersen, Lene Malmgaard, Søren C. Mogensen, and Søren R. Paludan*

Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark

Received 19 November 2004/ Accepted 5 April 2005

Elimination of viral infections is dependent on rapid recruitment and activation of leukocytes with antiviral activities to infected areas. Chemokines constitute a class of cytokines that have regulatory effects on leukocyte migration and activity. In this study we have studied the role of CC chemokine receptor 1 (CCR1) and CCR5 in host defense during a generalized herpes simplex virus type 2 (HSV-2) infection. Whereas both 4- and 8-week-old CCR1–/– mice resembled wild-type mice (C57BL/6) with respect to defense against the infection, significantly higher virus titers were seen in the livers and brains of 4-week-old CCR5–/– mice. At the age of 8 weeks, CCR5–/– were indistinguishable from wild-type mice and cleared the infection from liver and spleen. Although 4-week-old CCR5–/– mice were able to recruit natural killer (NK) cells to the site of infection, these cells had reduced cytotoxic activity compared to NK cells from wild-type mice. This was not due to lower production of alpha/beta interferon or interleukin-12, two well-described activators of cytotoxic activity in NK cells. We also noted that the spleens of young CCR5–/– mice did not increase in size during infection as did the spleens of wild-type and CCR1–/– mice. This observation was accompanied by impaired proliferation of CCR5–/– splenocytes (SCs) ex vivo. Moreover, migration of CD8+ T cells to the liver in response to infection was impaired in CCR5–/– mice, and adoptive transfer of SCs from CCR5–/– mice infected for 6 days into newly infected wild-type mice did not improve antiviral activity in the liver, in contrast to what was seen in mice receiving immune SCs from wild-type mice. Altogether, this study shows that CCR5 plays an age-dependent role in host defense against HSV-2 by supporting both the innate and adaptive immune response.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, The Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark. Phone: (45)89421766. Fax: (45)86196128. E-mail: srp{at}microbiology.au.dk.

Journal of Virology, August 2005, p. 9831-9841, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9831-9841.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Holst, P. J., Orskov, C., Qvortrup, K., Christensen, J. P., Thomsen, A. R. (2007). CCR5 and CXCR3 Are Dispensable for Liver Infiltration, but CCR5 Protects against Virus-Induced T-Cell-Mediated Hepatic Steatosis. J. Virol. 81: 10101-10112 [Abstract] [Full Text]  
  • Thapa, M., Kuziel, W. A., Carr, D. J. J. (2007). Susceptibility of CCR5-Deficient Mice to Genital Herpes Simplex Virus Type 2 Is Linked to NK Cell Mobilization. J. Virol. 81: 3704-3713 [Abstract] [Full Text]  
  • Zhang, J., Rao, E., Dioszegi, M., Kondru, R., DeRosier, A., Chan, E., Schwoerer, S., Cammack, N., Brandt, M., Sankuratri, S., Ji, C. (2007). The Second Extracellular Loop of CCR5 Contains the Dominant Epitopes for Highly Potent Anti-Human Immunodeficiency Virus Monoclonal Antibodies. Antimicrob. Agents Chemother. 51: 1386-1397 [Abstract] [Full Text]  
  • Sawaki, J., Tsutsui, H., Hayashi, N., Yasuda, K., Akira, S., Tanizawa, T., Nakanishi, K. (2007). Type 1 cytokine/chemokine production by mouse NK cells following activation of their TLR/MyD88-mediated pathways. Int Immunol 19: 311-320 [Abstract] [Full Text]  
  • Lederman, M. M., Penn-Nicholson, A., Cho, M., Mosier, D. (2006). Biology of CCR5 and its role in HIV infection and treatment.. JAMA 296: 815-826 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»