Mutations in the conserved carboxy-terminal hydrophobic region of glycoprotein gB affect infectivity of herpes simplex virus

Glycoprotein gB is the most highly conserved glycoprotein in the herpesviru s family and plays a critical role in virus entry and fusion, Glycoprotein gB of herpes simplex virus type 1 contains a hydrophobic stretch of 69 aa n ear the carboxy terminus that is essential for its biological activity, To determine the role(s) of specific amino acids in the carboxy-terminal hydro phobic region, a number of amino acids were mutagenized that are highly con served in this region within the gB homologues of the family Herpesviridae, Three conserved residues in the membrane anchor domain, namely A786, A790 and A791, as well as amino acids G743, G746, G766, G770 and P774, that are non-variant in Herpesviridae, were mutagenized, The ability of the mutant p roteins to rescue the infectivity of the gB-null virus, K082, in trans was measured by a complementation assay. All of the mutant proteins formed dime rs and were incorporated in virion particles produced in the complementatio n assay. Mutants G746N, G766N, F770S and P774L showed negligible complement ation of K082, whereas mutant G743R showed a reduced activity, Virion parti cles containing these four mutant glycoproteins also showed a markedly redu ced rate of entry compared to the wild-type. The results suggest that non-v ariant residues in the carboxy-terminal hydrophobic region of the gB protei n may be important in virus infectivity.