Herpes simplex virus type 1 evades the effects of antibody and complement in vivo.
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.
Department of Medicine, Division of Infectious Diseases, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
John M
JM
Lubinski
Ming
M
Jiang
Lauren
L
Hook
Yueh
Y
Chang
Chad
C
Sarver
Dimitrios
D
Mastellos
John D
JD
Lambris
Gary H
GH
Cohen
Roselyn J
RJ
Eisenberg
Harvey M
HM
Friedman
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006561:Herpes Simplex / Q000276:immunology / Q000401:mortality / Q000503:physiopathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009500:Neutralization Tests; D017452:Receptors, IgG / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014774:Virulence
D000914:Antibodies, Viral; D007141:Immunoglobulin Fc Fragments; D017452:Receptors, IgG; D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1; D003165:Complement System Proteins