Analysis of herpes simplex virus type 1 glycoprotein D nucleotide sequence in human herpes simplex encephalitis

Viral factors responsible for HSV neurovirulence in humans are still unknown. The aim of this work was to investigate the hypothesis that viral variants might contribute to the specific neurovirulence of some HSV strains. HSV-1 DNA was recovered from cerebrospinal fluid (CSF) in ten patients with HSV encephalitis (HSE) and the regions of HSV-1 gD gene corresponding to known antigenic sites were analyzed by direct sequencing of PCR products. Twenty-two mutations were found among a total of 6580 bp analyzed over a portion of 1000 bp of gD gene, of which 20 were silent whereas two conferred amino acid substitution. One missense mutation (E117D) was found in two CSF samples as well as in two control laboratory strains. The other one (A269T) was found in a single CSF sample, and lies within a region corresponding to a functionally essential antigenic site. These are the first mutations of the gene encoding gD of HSV identified in vivo in human encephalitis samples. Overall, the results argue against the role of gD in neurovirulence in humans.