Glycoprotein B plays a predominant role in mediating herpes simplex virus type 2 attachment and is required for entry and cell-to-cell spread.
Heparan sulfate moieties serve as receptors for initial binding of herpes simplex virus types 1 and 2 (HSV-1 and -2) to cells. Deletion of HSV-1 glycoprotein C (gC-1) but not HSV-2 gC (gC-2) results in virions with reduced specific binding activity (virus particles bound per cell) and specific infectivity (p.f.u. per particle), suggesting that for HSV-1, but not HSV-2, gC plays a major role in mediating virus attachment. To test the hypothesis that glycoprotein B (gB), the other heparin-binding glycoprotein, mediates HSV-2 attachment, HSV-2 viruses deleted in gB-2 alone or deleted in both gB-2 and gC-2 were constructed. These viruses were grown on complementing or non-complementing cells and were compared with parental HSV-2(G) or a gC-2-deleted HSV-2 mutant (with respect to ability to bind and infect cells). At equivalent input concentrations of purified virions, significantly fewer gB-2-deleted virions bound to cells compared to parental HSV-2(G) or virus grown on complementing cells. In addition, viruses deleted in gB-2 were non-infectious. No immediate early proteins were detected in cells infected with gB-2-deleted virus harvested from non-complementing Vero cells, whereas these proteins were readily detected 4 h post-infection in cells infected with virus grown on complementing cells or with parental viruses. Viruses deleted in gB-2 failed to spread cell to cell, as evidenced by the inability to form plaques. Together these studies demonstrate that gB-2 plays a key role in mediating HSV-2 attachment and is required for entry and cell-to-cell spread. This glycoprotein is an important target for development of novel antiviral drugs.
Department of Pediatrics and Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1657, New York, NY 10029, USA1.
Natalia
N
Cheshenko
Department of Pediatrics and Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1657, New York, NY 10029, USA1.
Betsy C
BC
Herold
D000818:Animals; D002522:Chlorocebus aethiops; D006561:Herpes Simplex / Q000821:virology; D018258:Herpesvirus 2, Human / Q000737:chemistry / Q000502:physiology*; D009154:Mutation; D014162:Transfection; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
D014759:Viral Envelope Proteins; C044525:glycoprotein B, herpes simplex virus type 2; C038535:glycoprotein gC, herpes simplex virus type 1