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Journal of Virology, January 2001, p. 569-578, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.569-578.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Modulation of Immunity against Herpes Simplex Virus Infection via Mucosal Genetic Transfer of Plasmid DNA Encoding Chemokines

Seong Kug Eo, Sujin Lee, Sangjun Chun, and Barry T. Rouse*

Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996

Received 24 July 2000/Accepted 20 October 2000

In this study, we examined the effects of murine chemokine DNA, as genetic adjuvants given mucosally, on the systemic and distal mucosal immune responses to plasmid DNA encoding gB of herpes simplex virus (HSV) by using the mouse model. The CC chemokines macrophage inflammatory protein 1beta (MIP-1beta ) and monocyte chemotactic protein 1 (MCP-1) biased the immunity to the Th2-type pattern as judged by the ratio of immunoglobulin isotypes and interleukin-4 cytokine levels produced by CD4+ T cells. The CXC chemokine MIP-2 and the CC chemokine MIP-1alpha , however, mounted immune responses of the Th1-type pattern, and such a response rendered recipients more resistant to HSV vaginal infection. In addition, MIP-1alpha appeared to act via the upregulation of antigen-presenting cell (APC) function and the expression of costimulatory molecules (B7-1 and B7-2), whereas MIP-2 enhanced Th1-type CD4+ T-cell-mediated adaptive immunity by increasing gamma interferon secretion from activated NK cells. Our results emphasize the value of using the mucosal route to administer DNA modulators such as chemokines that function as adjuvants by regulating the activity of innate immunity. Our findings provide new insight into the value of CXC and CC chemokines, which act on different innate cellular components as the linkage signals between innate and adaptive immunity in mucosal DNA vaccination.

* Corresponding author. Mailing address: Department of Microbiology, M409 Walters Life Sciences Building, The University of Tennessee, Knoxville, TN 37996-0845. Phone: (865) 974-4026. Fax: (865) 974-4007. E-mail: btr{at}utk.edu.

Journal of Virology, January 2001, p. 569-578, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.569-578.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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