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Journal of Virology, January 2001, p. 612-621, Vol. 75, No. 2
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.2.612-621.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Role of CD28/CD80-86 and CD40/CD154 Costimulatory
Interactions in Host Defense to Primary Herpes Simplex Virus
Infection
Kurt H.
Edelmann1 and
Christopher B.
Wilson1,2,*
Program in Molecular and Cellular
Biology,1 and Department of
Immunology,2 University of Washington,
Seattle, Washington 98195
Received 26 July 2000/Accepted 12 October 2000
Dependence of the primary antiviral immune response on
costimulatory interactions between CD28/CD80-86 and between CD40/CD154 (CD40 ligand) has been correlated with the extent of viral replication in two models of systemic infection, lymphocytic choriomeningitis virus
and vesicular stomatitis virus. To determine the role of these
costimulatory interactions in the context of an acute cytolytic, but
locally replicating viral infection, herpes simplex virus (HSV)
infection was assessed in mice that had the CD28/CD80-86 or CD40/CD154
interactions disrupted either genetically or with blocking reagents
(CTLA4Ig and MR1, respectively). CTLA4Ig treatment greatly reduced
paralysis-free survival during primary acute HSV infection. This
reflected an almost total ablation of the anti-HSV CD4+ and
CD8+ T-cell responses due to anergy and reduced cell
numbers, respectively. Disruption of CD40/CD154 interactions impaired
survival, but the effect was less severe than that observed in
CTLA4Ig-treated mice, with reductions observed in the CD4+
T-cell but not CD8+ T-cell responses. These two
costimulatory pathways functioned in part independently, since
disruption of both further impaired survival. The dependence on these
costimulatory interactions for the control of primary HSV infection may
represent a more widespread paradigm for nonsystemic viruses, which
have restricted sites of replication and which employ immunoevasive measures.
*
Corresponding author. Mailing address: Department of
Immunology, Box 357650, University of Washington, Seattle, WA 98195. Phone: (206) 543-1010. Fax: (206) 543-1013. E-mail:
cbwilson{at}u.washington.edu.
Journal of Virology, January 2001, p. 612-621, Vol. 75, No. 2
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.2.612-621.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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