Herpes simplex virus type 1 evades the effects of antibody and complement in vivo

John M. Lubinski, Ming Jiang, Lauren Hook, Yueh Chang, Chad Sarver, Dimitrios Mastellos, John D. Lambris, Gary H. Cohen, Roselyn J. Eisenberg, Harvey M. Friedman

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Herpes simplex virus type 1 (HSV-1) encodes a complement-interacting glycoprotein, gC, and an immuno-globulin 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.

Original languageEnglish (US)
Pages (from-to)9232-9241
Number of pages10
JournalJournal of Virology
Volume76
Issue number18
DOIs
StatePublished - Sep 2002
Externally publishedYes

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immune evasion
Immune Evasion
Human herpesvirus 1
Human Herpesvirus 1
complement
antibodies
Antibodies
Virulence
glycoproteins
Glycoproteins
virulence
immunoglobulin G
viruses
Complement C1q
Properdin
Vitamin D-Binding Protein
Defective Viruses
Virus Attachment
mutants
Blocking Antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

Lubinski, J. M., Jiang, M., Hook, L., Chang, Y., Sarver, C., Mastellos, D., ... Friedman, H. M. (2002). Herpes simplex virus type 1 evades the effects of antibody and complement in vivo. Journal of Virology, 76(18), 9232-9241. https://doi.org/10.1128/JVI.76.18.9232-9241.2002

Herpes simplex virus type 1 evades the effects of antibody and complement in vivo. / Lubinski, John M.; Jiang, Ming; Hook, Lauren; Chang, Yueh; Sarver, Chad; Mastellos, Dimitrios; Lambris, John D.; Cohen, Gary H.; Eisenberg, Roselyn J.; Friedman, Harvey M.

In: Journal of Virology, Vol. 76, No. 18, 09.2002, p. 9232-9241.

Research output: Contribution to journalArticle

Lubinski, JM, Jiang, M, Hook, L, Chang, Y, Sarver, C, Mastellos, D, Lambris, JD, Cohen, GH, Eisenberg, RJ & Friedman, HM 2002, 'Herpes simplex virus type 1 evades the effects of antibody and complement in vivo', Journal of Virology, vol. 76, no. 18, pp. 9232-9241. https://doi.org/10.1128/JVI.76.18.9232-9241.2002
Lubinski JM, Jiang M, Hook L, Chang Y, Sarver C, Mastellos D et al. Herpes simplex virus type 1 evades the effects of antibody and complement in vivo. Journal of Virology. 2002 Sep;76(18):9232-9241. https://doi.org/10.1128/JVI.76.18.9232-9241.2002
Lubinski, John M. ; Jiang, Ming ; Hook, Lauren ; Chang, Yueh ; Sarver, Chad ; Mastellos, Dimitrios ; Lambris, John D. ; Cohen, Gary H. ; Eisenberg, Roselyn J. ; Friedman, Harvey M. / Herpes simplex virus type 1 evades the effects of antibody and complement in vivo. In: Journal of Virology. 2002 ; Vol. 76, No. 18. pp. 9232-9241.
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