Phylogenetic comparison of exonic US4, US7 and UL44 regions of clinical herpes simplex virus type 1 isolates showed lack of association between their anatomic sites of infection and genotypic/sub genotypic classification

BACKGROUND: HSV-1 genome is a mosaic of recombinants. Clinical Herpes simplex virus -1 (HSV1) isolates were already genotyped as A, B and C types based on nucleotide variations at Unique Short (US) 4 (gG) and US 7 (gI) regions through phylogeny. Analysis of Glycoprotein C (gC) exon present on the Unique Long (UL) region had also revealed the existence of different genotypes. Glycoprotein C is mainly involved in initial viral attachment to heparan sulphate on host cell surface facilitating the virus's binding and penetration into cell. As the amount of heparan sulphate on the host cell surface varies according to the cell type, it is plausible that different genotypes bind differentially to cell types. Hence, this study was framed to determine the existence of novel genotypes/sub genotypes in the US or UL regions which could associate with clinical entities. RESULTS: All the twenty five isolates analyzed in this study were of genotype A as per their gG gene sequences. In case of gI gene, 16 out of 25 were found to be type A and the remaining nine were type B putative intergenic recombinants. Intragenic recombinations were also encountered in both the US genes, with gG possessing novel subgenotypes, arbitrarily designated A1 and A2. The 9 type B isolates of gI genes also branched out into 2 clades due to genetic variations. Glycoprotein C of UL region had two distinct genotypic clades α and β, whose topological distribution was significantly different from that of the US region. Neither the US nor UL regions, however, showed any preference among the genotypes to a specific anatomic site of infection. Even the non synonymous variations identified in the functional domain of gC, were not confined to a particular genotype/clinical entity. CONCLUSION: The analyses of the US and UL regions of the HSV-1 genome showed the existence of variegated genotypes in these two regions. In contrary to the documented literature, in which Asian strains were concluded as more conserved than European ones, our study showed the existence of a higher degree of variability among Indian strains. However, the identified novel genotypes and subgenotypes were not found associated with clinical entities.