In vivo immune evasion mediated by the herpes simplex virus type 1 immunoglobulin G Fc receptor.
Herpes simplex virus (HSV) glycoproteins gE and gI form an immunoglobulin G (IgG) Fc receptor (FcgammaR) 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 FcgammaR 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 FcgammaRs. NS-gE339 expresses gE and gI, is FcgammaR-, 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 FcgammaR does not bind murine IgG; therefore, the absence of an FcgammaR 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 FcgammaR- 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 FcgammaR 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 FcgammaR enables the virus to evade antibody attack in vivo, which likely explains why antibodies are relatively ineffective against HSV infection.
Nagashunmugam
T
T
Infectious Diseases Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6073, USA.
Lubinski
J
J
Wang
L
L
Goldstein
L T
LT
Weeks
B S
BS
Sundaresan
P
P
Kang
E H
EH
Dubin
G
G
Friedman
H M
HM
D000818:Animals; D002522:Chlorocebus aethiops; D005260:Female; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D017452:Receptors, IgG / Q000502:physiology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000502:physiology
D007074:Immunoglobulin G; D017452:Receptors, IgG; D014759:Viral Envelope Proteins; C044768:glycoprotein E, herpes simplex virus type 1