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Journal of Virology, October 1998, p. 8257-8263, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Herpes Simplex Virus Type 1 Glycoprotein gC Mediates Immune Evasion In Vivo

John M. Lubinski,1 Liyang Wang,1 Athena M. Soulika,2 Reinhard Burger,3 Rick A. Wetsel,4,dagger Harvey Colten,4,Dagger Gary H. Cohen,5 Roselyn J. Eisenberg,6 John D. Lambris,2 and Harvey M. Friedman1,*

Departments of Medicine1 and Pathology,2 School of Medicine, Department of Microbiology, School of Dental Medicine,5 and Veterinary Medicine,6 University of Pennsylvania, Philadelphia, Pennsylvania; Robert Koch Institut, Berlin, Germany3; and Department of Pediatrics, School of Medicine, Washington University, St. Louis, Missouri4

Received 12 May 1998/Accepted 25 June 1998

Many microorganisms encode proteins that interact with molecules involved in host immunity; however, few of these molecules have been proven to promote immune evasion in vivo. Herpes simplex virus type 1 (HSV-1) glycoprotein C (gC) binds complement component C3 and inhibits complement-mediated virus neutralization and lysis of infected cells in vitro. To investigate the importance of the interaction between gC and C3 in vivo, we studied the virulence of a gC-null strain in complement-intact and C3-deficient animals. Using a vaginal infection model in complement-intact guinea pigs, we showed that gC-null virus grows to lower titers and produces less severe vaginitis than wild-type or gC rescued virus, indicating a role for gC in virulence. To determine the importance of complement, studies were performed with C3-deficient guinea pigs; the results demonstrated significant increases in vaginal titers of gC-null virus, while wild-type and gC rescued viruses showed nonsignificant changes in titers. Similar findings were observed for mice where gC null virus produced significantly less disease than gC rescued virus at the skin inoculation site. Proof that C3 is important was provided by studies of C3 knockout mice, where disease scores of gC-null virus were significantly higher than in complement-intact mice. The results indicate that gC-null virus is approximately 100-fold (2 log10) less virulent that wild-type virus in animals and that gC-C3 interactions are involved in pathogenesis.

* Corresponding author. Mailing address: 536 Johnson Pavilion, University of Pennsylvania, Philadelphia, PA 19104-6073. Phone: (215) 662-2473. Fax: (215) 349-5111. E-mail: hfriedma{at}mail.med.upenn.edu.

dagger Present address: Institute of Molecular Medicine for Prevention of Human Diseases, University of Texas, Houston, TX 77030.

Dagger Present address: Northwestern University Medical School, Chicago, IL 60611.

Journal of Virology, October 1998, p. 8257-8263, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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