Human herpesvirus 6B genome sequence: Coding content and comparison with human herpesvirus 6A

Human herpesvirus 6 variants A and B (HHV-6A and HHV-6B) are closely relate d viruses that can be readily distinguished by comparison of restriction en donuclease profiles and nucleotide sequences. The viruses are similar with respect to genomic and genetic organization, and their genomes cross-hybrid ize extensively, but they differ in biological and epidemiologic features. Differences include infectivity of T-cell lines, patterns of reactivity wit h monoclonal antibodies, and disease associations. Here we report the compl ete genome sequence of HHV-6B strain Z29 I[HHV-6B(Z29)], describe its genet ic content, and present an analysis of the relationships between HHV-6A and HHV-6B, As sequenced, the HHV-6B(Z29) genome is 162,114 bp long and is com posed of a 144,528-bp unique segment (11) bracketed by 8,793-bp direct repe ats (DR). The genomic sequence allows prediction of a total of 119 unique o pen reading frames (ORFs), 9 of which are present only in HHV-6B, Splicing is predicted in 11 genes, resulting in the 119 ORFs composing 97 unique gen es. The overall nucleotide sequence identity between HHV-6A and HHV-6B is 9 0%. The most divergent regions are DR and the right end of U, spanning ORFs U86 to U100. These regions have 85 and 72% nucleotide sequence identity, r espectively. The amino acid sequences of 13 of the 17 ORFs at the right end of U differ by more than 10%, with the notable exception of U94, the adeno -associated virus type 2 rep homolog, which differs by only 2.4%. This regi on also includes putative cis-acting sequences that are likely to be involv ed in transcriptional regulation of the major immediate-early locus, The ca talog of variant-specific genetic differences resulting from our comparison of the genome sequences adds support to previous data indicating that HHV- 6A and HHV-6B are distinct herpesvirus species.