Sequence Variation in the Herpes Simplex Virus US1 Ocular Virulence Determinant

PURPOSE. The herpes simplex virus type 1 (HSV-1) U(S)1 gene encodes host-range and ocular virulence determinants. Mutations in U(S)1 affecting virulence are known in strain OD4, but the genomic variation across several strains is not known. The goal was to determine the degree of sequence variation in the gene from several ocular HSV isolates. METHODS. The U(S)1 gene from six ocular HSV-1 isolates, as well as strains KOS and F, were sequenced, and bioinformatics analyses were applied to the data. RESULTS. Strains 17, F, CJ394, and CJ311 had identical amino acid sequences. With the other strains, most of the variability was concentrated in the amino-terminal third of the protein. MEME analysis identified a 63-residue core sequence (motif 1) present in all alpha-herpesvirus U(S)1 homologs that were located in a region identified as structured. Ten amino acids were absolutely conserved in all the alpha-herpesvirus U(S)1 homologs and were all located in the central core. Consensus-binding motifs for cyclin-dependent kinases and pocket proteins were also identified. CONCLUSIONS. These results suggest that significant sequence variation exists in the U(S)1 gene, that the alpha 22 protein contains a conserved central core region with structurally variable regions at the amino-and carboxyl termini, that 10 amino acids are conserved in alpha-herpes U(S)1 homologs, and that additional host proteins may interact with the HSV-1 U(S)1 and U(S)1.5 proteins. This information will be valuable in designing further studies on structure-function relationships and on the role these play in host-range determination and keratitis. (Invest Ophthalmol Vis Sci. 2011;52:4630-4638) DOI:10.1167/iovs.10-7032