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Journal of Virology, September 2002, p. 9232-9241, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9232-9241.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Herpes Simplex Virus Type 1 Evades the Effects of Antibody and Complement In Vivo

John M. Lubinski,1 Ming Jiang,1 Lauren Hook,1 Yueh Chang,1 Chad Sarver,1 Dimitrios Mastellos,2 John D. Lambris,2 Gary H. Cohen,3 Roselyn J. Eisenberg,4 and Harvey M. Friedman1*

Department of Medicine, Division of Infectious Diseases,1 Department of Pathology and Laboratory Medicine, School of Medicine,2 Department of Microbiology, School of Dental Medicine,3 Department of Microbiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 191044

Received 19 April 2002/ Accepted 12 June 2002

Herpes simplex virus type 1 (HSV-1) encodes a complement-interacting glycoprotein, gC, and an immunoglobulin G (IgG) Fc binding glycoprotein, gE, that mediate immune evasion by affecting multiple aspects of innate and acquired immunity, including interfering with complement components C1q, C3, C5, and properdin and blocking antibody-dependent cellular cytotoxicity. Previous studies evaluated the individual contributions of gC and gE to immune evasion. Experiments in a murine model that examines the combined effects of gC and gE immune evasion on pathogenesis are now reported. Virulence of wild-type HSV-1 is compared with mutant viruses defective in gC-mediated C3 binding, gE-mediated IgG Fc binding, or both immune evasion activities. Eliminating both activities greatly increased susceptibility of HSV-1 to antibody and complement neutralization in vitro and markedly reduced virulence in vivo as measured by disease scores, virus titers, and mortality. Studies with C3 knockout mice indicated that other activities attributed to these glycoproteins, such as gC-mediated virus attachment to heparan sulfate or gE-mediated cell-to-cell spread, do not account for the reduced virulence of mutant viruses. The results support the importance of gC and gE immune evasion in vivo and suggest potential new targets for prevention and treatment of HSV disease.

* Corresponding author. Mailing address: 502 Johnson Pavilion, University of Pennsylvania, Philadelphia, PA 19104-6073. Phone: (215) 662-3557. Fax: (215) 349-5111. E-mail: hfriedma{at}mail.med.upenn.edu.

Journal of Virology, September 2002, p. 9232-9241, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9232-9241.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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