Blocking Antibody Access to Neutralizing Domains on Glycoproteins Involved in Entry as a Novel Mechanism of Immune Evasion by Herpes Simplex Virus Type 1 Glycoproteins C and E
- 15 July 2008
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 82 (14), 6935-6941
- https://doi.org/10.1128/jvi.02599-07
Abstract
Herpes simplex virus type 1 (HSV-1) glycoprotein C (gC) blocks complement activation, and glycoprotein E (gE) interferes with IgG Fc-mediated activities. While evaluating gC- and gE-mediated immune evasion in human immunodeficiency virus (HIV)-HSV-1-coinfected subjects, we noted that antibody alone was more effective at neutralizing a strain with mutations in gC and gE (gC/gE) than a wild-type (WT) virus. This result was unexpected since gC and gE are postulated to interfere with complement-mediated neutralization. We used pooled human immunoglobulin G (IgG) from HIV-negative donors to confirm the results and evaluated mechanisms of the enhanced antibody neutralization. We demonstrated that differences in antibody neutralization cannot be attributed to the concentrations of HSV-1 glycoproteins on the two viruses or to the absence of an IgG Fc receptor on the gC/gE mutant virus or to enhanced neutralization of the mutant virus by antibodies that target only gB, gD, or gH/gL, which are the glycoproteins involved in virus entry. Since sera from HIV-infected subjects and pooled human IgG contain antibodies against multiple glycoproteins, we determined whether differences in neutralization become apparent when antibodies to gB, gD, or gH/gL are used in combination. Neutralization of the gC/gE mutant was greatly increased compared that of WT virus when any two of the antibodies against gB, gD, or gH/gL were used in combination. These results suggest that gC and gE on WT virus provide a shield against neutralizing antibodies that interfere with gB-gD, gB-gH/gL, or gD-gH/gL interactions and that one function of virus neutralization is to prevent interactions between these glycoproteins.Keywords
This publication has 33 references indexed in Scilit:
- Bimolecular complementation reveals that glycoproteins gB and gH/gL of herpes simplex virus interact with each other during cell fusionProceedings of the National Academy of Sciences of the United States of America, 2007
- Herpes Simplex Virus Type 1 Glycoprotein E Is Required for Axonal Localization of Capsid, Tegument, and Membrane GlycoproteinsJournal of Virology, 2005
- Implications for herpes simplex virus vaccine strategies based on antibodies produced to herpes simplex virus type 1 glycoprotein gC immune evasion domainsVaccine, 2005
- Blocking Immune Evasion as a Novel Approach for Prevention and Treatment of Herpes Simplex Virus InfectionJournal of Virology, 2003
- Herpes simplex virus type 1 can either suppress or enhance human immunodeficiency virus type 1 replication in CD4‐positive T lymphocytesJournal of Medical Virology, 2003
- Herpes Simplex Virus Type 1 Evades the Effects of Antibody and Complement In VivoJournal of Virology, 2002
- Risk of Human Immunodeficiency Virus Infection in Herpes Simplex Virus Type 2–Seropositive Persons: A Meta‐analysisThe Journal of Infectious Diseases, 2002
- Virologic Characteristics of Subclinical and Symptomatic Genital Herpes InfectionsNew England Journal of Medicine, 1995
- Epidemiological SynergySexually Transmitted Diseases, 1992
- Glycoprotein C of herpes simplex virus 1 acts as a receptor for the C3b complement component on infected cellsNature, 1984