Herpes simplex virus type 1 and 2 glycoprotein C prevents complement-mediated neutralization induced by natural immunoglobulin M antibody

Lauren M. Hook, John M. Lubinski, Ming Jiang, Michael K. Pangburn, Harvey M. Friedman

Research output: Contribution to journalArticle

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Abstract

Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) binds complement component C3b and protects virus from complement-mediated neutralization. Differences in complement interacting domains exist between gC of HSV-1 (gC1) and HSV-2 (gC2), since the amino terminus of gC1 blocks complement C5 from binding to C3b, while gC2 fails to interfere with this activity. We previously reported that neutralization of HSV-1 gC-null virus by HSV antibody-negative human serum requires activation of C5 but not of downstream components of the classical complement pathway. In this report, we evaluated whether activation of C5 is sufficient to neutralize HSV-2 gC-null virus, or whether formation of the membrane attack complex by C6 to C9 is required for neutralization. We found that activation of the classical complement pathway up to C5 was sufficient to neutralize HSV-2 gC-null virus by HSV antibody-negative human serum. We evaluated the mechanisms by which complement activation occurred in seronegative human serum. Interestingly, natural immunoglobulin M antibodies bound to virus, which triggered activation of C1q and the classical complement pathway. HSV antibody-negative sera obtained from four individuals differed over an approximately 10-fold range in their potency for complement-mediated virus neutralization. These findings indicate that humans differ in the ability of their innate immune systems to neutralize HSV-1 or HSV-2 gC-null virus and that a critical function of gC1 and gC2 is to prevent C5 activation.

Original languageEnglish (US)
Pages (from-to)4038-4046
Number of pages9
JournalJournal of Virology
Volume80
Issue number8
DOIs
StatePublished - Apr 2006
Externally publishedYes

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Human herpesvirus 2
Human herpesvirus 1
immunoglobulin M
Human Herpesvirus 2
Human Herpesvirus 1
neutralization
Immunoglobulin M
glycoproteins
complement
antibodies
Antibodies
Viruses
viruses
Classical Complement Pathway
Serum
Complement C5
glycoprotein gC, herpes simplex virus type 1
Complement C3b
Complement Membrane Attack Complex
neutralization tests

ASJC Scopus subject areas

  • Immunology

Cite this

Herpes simplex virus type 1 and 2 glycoprotein C prevents complement-mediated neutralization induced by natural immunoglobulin M antibody. / Hook, Lauren M.; Lubinski, John M.; Jiang, Ming; Pangburn, Michael K.; Friedman, Harvey M.

In: Journal of Virology, Vol. 80, No. 8, 04.2006, p. 4038-4046.

Research output: Contribution to journalArticle

Hook, Lauren M. ; Lubinski, John M. ; Jiang, Ming ; Pangburn, Michael K. ; Friedman, Harvey M. / Herpes simplex virus type 1 and 2 glycoprotein C prevents complement-mediated neutralization induced by natural immunoglobulin M antibody. In: Journal of Virology. 2006 ; Vol. 80, No. 8. pp. 4038-4046.
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