Analysis of a Membrane Interacting Region af Herpes Simplex Virus Type1 Glycoprotein H

Glycoprotein H (gH) of herpes simplex virus type I (HSV-1) is involved in the complex mechanism of membrane fusion of the viral envelope with the host cell. Membrane interacting regions and potential fusion peptides have been identified in HSV-1 gH as well as gB. Due to the complex fusion mechanism of HSV-1 which requires 4 viral glycoproteins, and since there are only structural data for gB and gD, many questions regarding the mechanism by which HSV-1 fuses its envelope with the host cell membrane remain unresolved. Previous studies have shown that peptides derived from certain regions of gH have the potential to interact with membranes, and based on these findings we have generated a set of peptides containing mutations in one of these domains, gH626-644, to investigate further the functional role of this region. Using a combination of biochemical, spectroscopic and nuclear magnetic resonance techniques, we showed that the alpha-helical nature of this stretch of amino acids in gH is important for membrane interaction, and that the aromatic residues, tryptophan and tyrosine are critical for induction of fusion.