Genotyping of herpes simplex virus type 1 by whole-genome sequencing

A previous phylogenetic analysis based on 32 full-length sequences of herpes simplex virus type 1 (HSV-1) suggested three major phylogenetic groups (phylogroups) with distinct geographic distribution: (1) western strains from Europe and North America, (2) isolates from Asia and one American strain and (3) isolates from Africa only. Here, we sequenced the genomes of additional 10 clinical HSV-1 isolates from Germany, and subsequently compared these sequences to 40 published HSV-1 genomes. The present data demonstrate that HSV-1 is the most diverse human alphaherpesvirus (mean pairwise p-distance of 0.756 %) and confirm the tripartite tree. However, as the German isolates cluster with strains of both phylogroups I and II, it is demonstrated that the latter is also present in Europe and thus is a Eurasian phylogroup. Tree-order scans indicate that HSV-1 evolution is massively influenced by recombination including all investigated strains regardless of the areal distribution of the phylogroups. Numerous recombination events in the evolution of HSV-1 may also influence genotyping as the present HSV-1 genotyping schemes do not yield results consistent with phylogroup classification. Genotyping of HSV-1 is currently based on analyses of intragenic sequence polymorphisms of US2, glycoprotein G (gG, US4) and gI (US7). Each of the 10 German HSV-1 isolates displayed a different US2/gG/gI-genotype combination, but clustered either in phylogroup I or II. In conclusion, the phylogroup concept provides a HSV-1 typing scheme that largely reflects human migration history, whereas the analysis of single-nucleotide polymorphisms fails to render significant biological properties, but allows description of individual genetic traits.