Human Herpesvirus 6B Genome Sequence: Coding Content and Comparison with Human Herpesvirus 6A

Abstract

Human herpesvirus 6 variants A and B (HHV-6A and HHV-6B) are closely related viruses that can be readily distinguished by comparison of restriction endonuclease profiles and nucleotide sequences. The viruses are similar with respect to genomic and genetic organization, and their genomes cross-hybridize extensively, but they differ in biological and epidemiologic features. Differences include infectivity of T-cell lines, patterns of reactivity with monoclonal antibodies, and disease associations. Here we report the complete genome sequence of HHV-6B strain Z29 [HHV-6B(Z29)], describe its genetic 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 composed of a 144,528-bp unique segment (U) bracketed by 8,793-bp direct repeats (DR). The genomic sequence allows prediction of a total of 119 unique open 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 genes. The overall nucleotide sequence identity between HHV-6A and HHV-6B is 90%. 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, respectively. 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 region also includes putative cis-acting sequences that are likely to be involved in transcriptional regulation of the major immediate-early locus. The catalog 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.

Human herpesvirus 6A induces apoptosis of HSB-2 cells via a mitochondrion-related caspase pathway

“…HHV-6 is a member of the Betaherpesvirinae subfamily. Two major subgroups with distinct genetic, immunological and virologic characteristics have been named as HHV-6A and HHV-6B [24][25][26][27][28] . Ichimi et al reported that in cord blood lymphocytes, HHV-6 induced apoptosis by an unknown mechanism, which was independent of death receptors [29] .…”

Differential tropism of human herpesvirus 6 (HHV-6) variants and induction of latency by HHV-6A in oligodendrocytes

“…The genomes of HHV-6A and HHV-6B range in length from 160 to 170 kb and encode approximately 100 proteins . The overall nucleotide sequence identity between HHV-6A and HHV-6B is approximately 90% (Dominguez et al, 1999). Eighteen open reading frames are unique to either HHV-6A or HHV-6B.…”

Infection and Multiple Sclerosis

“…The genomes of HHV-6A and HHV-6B range in length from 160-170 kbp and encode approximately 100 proteins [ 144]. The overall nucleotide sequence identity between HHV-6A and HHV-6B is approximately 90% [145]. Of the genes with less than 70% identity between the two variants, all but one (U47) were found in the immediate-early region [145].…”

“…The overall nucleotide sequence identity between HHV-6A and HHV-6B is approximately 90% [145]. Of the genes with less than 70% identity between the two variants, all but one (U47) were found in the immediate-early region [145]. Eighteen open reading frames are unique to either HHV-6A or HHV-6B.…”

“…Due to the close sequence identities between the two viruses and the absence of serological assays that can easily discriminate between the two variants, HHV-6A and HHV-6B are often treated as a single virus. However, it has been argued that differences in the biology, cellular tropisms, and restriction endonuclease profiles of the two variants are sufficient to classify them as distinct herpesviruses rather than as vairiants of the same virus [ 145,144]. The HHV-6B variant has been identified as the causative agent of exanthem subitum and accounts for the majority of symptomatic HHV-6 infections in infants.…”