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J Virol, July 1998, p. 5351-5359, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

In Vivo Immune Evasion Mediated by the Herpes Simplex Virus Type 1 Immunoglobulin G Fc Receptor

Thandavarayan Nagashunmugam, John Lubinski, Liyang Wang, Lester T. Goldstein, Benjamin S. Weeks,dagger Periasamy Sundaresan,Dagger Eugene H. Kang,§ Gary Dubin,parallel and Harvey M. Friedman*

Infectious Diseases Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6073

Received 29 December 1997/Accepted 25 March 1998

Herpes simplex virus (HSV) glycoproteins gE and gI form an immunoglobulin G (IgG) Fc receptor (Fcgamma R) that binds the Fc domain of human anti-HSV IgG and inhibits Fc-mediated immune functions in vitro. gE or gI deletion mutant viruses are avirulent, probably because gE and gI are also involved in cell-to-cell spread. In an effort to modify Fcgamma R activity without affecting other gE functions, we constructed a mutant virus, NS-gE339, that has four amino acids inserted into gE within the domain homologous to mammalian IgG Fcgamma Rs. NS-gE339 expresses gE and gI, is Fcgamma R-, and does not participate in antibody bipolar bridging since it does not block activities mediated by the Fc domain of anti-HSV IgG. In vivo studies were performed with mice because the HSV-1 Fcgamma R does not bind murine IgG; therefore, the absence of an Fcgamma R should not affect virulence in mice. NS-gE339 causes disease at the skin inoculation site comparably to wild-type and rescued viruses, indicating that the Fcgamma R- mutant virus is pathogenic in animals. Mice were passively immunized with human anti-HSV IgG and then infected with mutant or wild-type virus. We postulated that the HSV-1 Fcgamma R should protect wild-type virus from antibody attack. Human anti-HSV IgG greatly reduced viral titers and disease severity in NS-gE339-infected animals while having little effect on wild-type or rescued virus. We conclude that the HSV-1 Fcgamma R enables the virus to evade antibody attack in vivo, which likely explains why antibodies are relatively ineffective against HSV infection.


* Corresponding author. Mailing address: 536 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.

dagger Present address: Adelphi University, Biology Department, Garden City, NY 11530.

Dagger Present address: c/o Robert L. Martuza, Molecular Neurosurgery Laboratory, Georgetown Medical University, Washington, DC 20007.

§ Present address: Department of Surgery, Philadelphia, PA 19104-6073.

parallel Present address: SmithKline Beecham Biologicals, B-1330 Rixensart, Belgium.


J Virol, July 1998, p. 5351-5359, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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