Genome sequence of herpes simplex virus 1 strain

The herpes simplex virus 1 (HSV-1) strainMcKrae is highly virulent compared to other wild-type strains of HSV-1. To help us better understand the genetic determinants that lead to differences in the pathogenicity of McKrae and other HSV-1 strains, we sequenced its genome. Comparing the sequence of McKrae’s genome to that of strain 17 revealed that the genomes differ by at least 752 single nucleotide polymorphisms (SNPs) and 86 insertion/deletion events (indels). Although the majority of these poly-morphisms reside in noncoding regions, 241 SNPs and 10 indels alter the protein-coding sequences of 58 open reading frames. Some of these variations are expected to contribute to the pathogenic phenotype of McKrae. Herpes simplex virus 1 (HSV-1) is a double-stranded DNA,enveloped virus of theHerpesviridae family. HSV-1 infections can be asymptomatic or cause cold sores, corneal ulcerations, or life-threatening encephalitis (9). Studies examining a variety of HSV-1 strains show a broad spectrum of virulent and pathogenic phenotypes. Notably, the HSV-1 strain McKrae reactivates at a high frequency and is more neurovirulent in animal models than other strains of HSV-1 (4, 7, 8, 10, 11). Because viral determinants that contribute to McKrae’s in vivo phenotypes are largely un-known, we sequenced its genome