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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,
Periasamy
Sundaresan,
Eugene H.
Kang,§
Gary
Dubin,
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 (Fc
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
Fc
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 Fc
Rs.
NS-gE339 expresses gE and gI, is Fc
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 Fc
R does not bind
murine IgG; therefore, the absence of an Fc
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 Fc
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
Fc
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 Fc
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.

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

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.

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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