Journal article
Monoclonal Antibodies to Distinct Sites on Herpes Simplex Virus (HSV) Glycoprotein D Block HSV Binding to HVEM
Journal of virology, Vol.72(5), pp.3595-3601
05/1998
Handle:
https://hdl.handle.net/2376/104689
PMCID: PMC109580
PMID: 9557640
Abstract
HVEM (for herpesvirus entry mediator) is a member of the tumor necrosis factor receptor superfamily and mediates entry of many strains of herpes simplex virus (HSV) into normally nonpermissive Chinese hamster ovary (CHO) cells. We used sucrose density centrifugation to demonstrate that purified HSV-1 KOS virions bind directly to a soluble, truncated form of HVEM (HVEMt) in the absence of any other cell-associated components. Therefore, HVEM mediates HSV entry by serving as a receptor for the virus. We previously showed that soluble, truncated forms of HSV glycoprotein D (gDt) bind to HVEMt in vitro. Here we show that antibodies specific for gD, but not the other entry glycoproteins gB, gC, or the gH/gL complex, completely block HSV binding to HVEM. Thus, virion gD is the principal mediator of HSV binding to HVEM. To map sites on virion gD which are necessary for its interaction with HVEM, we preincubated virions with gD-specific monoclonal antibodies (MAbs). MAbs that recognize antigenic sites Ib and VII of gD were the only MAbs which blocked the HSV-HVEM interaction. MAbs from these two groups failed to coprecipitate HVEMt in the presence of soluble gDt, whereas the other anti-gD MAbs coprecipitated HVEMt and gDt. Previous mapping data indicated that site VII includes amino acids 11 to 19 and site Ib includes 222 to 252. The current experiments indicate that these sites contain residues important for HSV binding to HVEM. Group Ib and VII MAbs also blocked HSV entry into HVEM-expressing CHO cells. These results suggest that the mechanism of neutralization by these MAbs is via interference with the interaction between gD in the virus and HVEM on the cell. Group Ia and II MAbs failed to block HSV binding to HVEM yet still neutralized HVEM-mediated entry, suggesting that these MAbs block entry at a step other than HVEM binding.
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Details
- Title
- Monoclonal Antibodies to Distinct Sites on Herpes Simplex Virus (HSV) Glycoprotein D Block HSV Binding to HVEM
- Creators
- Anthony V Nicola - Department of MicrobiologyManuel Ponce de Leon - Department of MicrobiologyRuliang Xu - Department of MicrobiologyWangfang Hou - Department of MicrobiologyJ. Charles Whitbeck - Department of MicrobiologyClaude Krummenacher - Department of MicrobiologyRebecca I Montgomery - Department of MicrobiologyPatricia G Spear - Department of MicrobiologyRoselyn J Eisenberg - Department of MicrobiologyGary H Cohen - Department of Microbiology
- Publication Details
- Journal of virology, Vol.72(5), pp.3595-3601
- Academic Unit
- Veterinary Microbiology and Pathology, Department of
- Publisher
- American Society for Microbiology
- Identifiers
- 99900546956901842
- Language
- English
- Resource Type
- Journal article