Sequence and comparative analysis of the genome of HSV-1 strain McKrae

Abstract

Ocular infection by HSV-1 strain McKrae is neurovirulent in both mice and rabbits and causes fatal encephalitis in approximately 50% of animals. In addition, it spontaneously reactivates with high frequency relative to other HSV-1 strains in rabbits. We sequenced the McKrae strain genome and compared its coding protein sequences with those of six other HSV-1 strains. Most of the 74 predicted protein sequences are conserved; only eleven are less than 98% conserved. Eight proteins were identified to be unique for McKrae based on sequence homology bit score ratio (BSR). These include five proteins showing significant variations (RL1, RS1, UL49A, US7 and US11), two truncated proteins (UL36 and UL56) and one (US10) containing an extended open reading frame. The McKrae strain also has unique features in its 'a' sequence and non-coding sequences, such as LAT and miRNA. These data are indicative of strain variation but need further work to connect observed differences with phenotype effects.

Evolution and Diversity in Human Herpes Simplex Virus Genomes

“…For this reason, a greater number of strains from Kenya than from other countries was included for sequencing. To augment the global diversity in our analyses, these 20 genomes were supplemented by six previously published sequences from the United States and United Kingdom (Table 1) (29,43,45,(47)(48)(49)(50).…”

“…This makes determining their sizes a challenge, since a population of viral DNA used for sequencing may contain genomes with different lengths of a given SSR and high-throughput sequencing reads rarely span the full length of the larger SSRs. Originally, the lengths of these SSRs were determined in the HSV-1 reference genome by Sanger sequencing of cloned genome fragments that spanned each SSR (44,45); all high-throughput-sequenced genomes since then have left one or more of these SSRs indeterminate (13,29,30,(48)(49)(50). In the newly sequenced genomes, we marked the subset of these SSRs that cannot be determined by high-throughput sequencing as gaps (Fig.…”

“…Six previously sequenced HSV-1 strains were included in the analysis, with data derived from each strain's GenBank record and associated publication(s). The publications describing these sequenced genomes are as follows, and the accession numbers for each sequence are listed in Table 1: 17 (43)(44)(45)(46), HF10 (47), F (29), H129 (29), KOS (48), and McKrae (49,50). Since the geographic origin of HSV-1 strains is considered in our analyses, the publications describing the first isolation and geographic origin of each strain are as follows: 17 (51), F (52), H129 (53), KOS (54), and McKrae (55).…”

“…Both records for KOS are listed in Table 1; we used the record published under accession number JQ673480 for the genomewide alignment (48). For McKrae, we used the genome sequence from the record published under accession number JQ730035 (49). Three coding frameshifts deleterious for growth in vivo (in UL36, UL56, and US10) were found in the record under accession number JQ730035 for McKrae but not the alternate record under accession number JX142173; we used the latter amino acid sequence in these cases (49,50).…”

“…For McKrae, we used the genome sequence from the record published under accession number JQ730035 (49). Three coding frameshifts deleterious for growth in vivo (in UL36, UL56, and US10) were found in the record under accession number JQ730035 for McKrae but not the alternate record under accession number JX142173; we used the latter amino acid sequence in these cases (49,50). Seven substantially incomplete genomes (of U.S. origin) were not included in the comparisons because of a large number of gaps in both coding and noncoding regions (30).…”