The properties and sequence of glycoprotein H of herpes simplex virus type 1

Abstract

The map position of the coding sequence of glycoprotein H of herpes simplex virus type 1 was determined by marker transfer studies in which DNA fragments cloned from a virus resistant to neutralisation by an anti-gH monoclonal antibody were used to transfer antibody resistance to wild type virus DNA following cotransfection. The gH coding sequence was mapped to the BglII “m” fragment of HSV-1 DNA (map coordinates 0.27–0.312), confirming the map position previously determined by intertypic recombinant analysis ( Buckmaster et al., 1984). The complete nucleotide sequence of the BglII “m” fragment revealed two large open reading frames in addition to the thymidine kinase gene. The open reading frame lying immediately 3′ of the thymidine kinase gene has a predicted translation product with the features of a large glycoprotein. This open reading frame translates to an amino acid sequence of 90,323 mol wt with a signal peptide, a membrane anchor sequence, a large external domain containing potential N-glycosylation sites, and a charged C- terminal cytoplasmic domain. We suppose that this amino acid sequence corresponds to gH of HSV-1, and A. Davison (personal communication) has noted the existence of homologous glycoproteins predicted from the nucleotide sequences of Varicella-zoster virus and Epstein-Barr virus. The properties of monoclonal antibody LP11, directed against gH show remarkable similarities to the properties for gD antibodies. LP11 efficiently neutralises virus infectivity, blocks cell fusion by syncytial virus strains, and inhibits the formation of plaques when added to cell monolayers after infection. These similarities in antibody activity imply functional relatedness between gH and gD of herpes simplex virus.