Evolution and Diversity in Human Herpes Simplex Virus Genomes

Evolution and Diversity in Human Herpes Simplex Virus Genomes

Evolution and Diversity in Human Herpes Simplex Virus Genomes
Localization and conservation of SSRs in HSV-1 strains. To identify possible commonalities in HLA binding preferences, we quantify these using a novel measure termed “targeting efficiency,” which captures the correlation between HLA-peptide binding affinities and the conservation of the targeted proteomic regions. A high-fidelity nested reverse transcription (RT)-PCR assay was developed, and validation using control transcripts of known copy number indicated a detection limit of 3 copies of viral RNA/reaction. Sixteen substitutions were nonsynonymous, the majority of which were clustered within surface-expressed proteins. Green-shaded blocks above the alignment indicate known functional regions of the protein (146–152). (C to E) Similar plots depict nucleotide distribution in unique versus repeated regions of human beta- (human cytomegalovirus [HCMV]) and gammaherpesviruses (Epstein-Barr virus [EBV] and Kaposi’s sarcoma-associated herpesvirus [KSHV]). Highlighted residues fall into the H1 and H2 domains described previously (77).

SSRs are color coded to distinguish those for which length is conserved in at least half of the 26 strains (green) versus those for which length is variable in a majority of strains (orange). The prototype VZV sequence contains nearly 125,000 base pairs, divided into 70 open reading frames. These TRs join together in circularized genomes. However, only two full-length HSV-2 genomes have been reported.

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