Genetic content of a 20.9 kb segment of human herpesvirus 6B strain Z29 spanning the homologs of human herpesvirus 6A genes U40-57 and containing the origin of DNA replication.

A continuous 20.9 kb sequence from human herpesvirus 6 variant B (HHV-6B) strain Z29 (GenBank accession number L16947) is genetically colinear with a discrete segment of the human cytomegalovirus (HCMV) UL region and with HHV-6 variant A (HHV-6A). Short nucleotide sequence determinations at multiple sites within an 8.5 kb region immediately 3' to the 20.9 kb contig revealed additional colinearity between HHV-6B, HCMV and HHV-6A. Homology studies with the predicted peptide sequences from 11 complete and 12 partial HHV-6B open reading frames (ORFs) revealed that most encode proteins conserved to varying degrees in all previously sequenced primate herpesviruses. HHV-6B homologs were identified for the HSV-1 ICP18.5, ICP8, UL52, UL24, UL25 and major capsid protein. Several HHV-6B proteins had limited amino acid similarity to their positional homologs in other herpesviruses. Each gene identified is highly homologous to its HHV-6A counterpart, including two unique HHV-6 genes predicted to encode membrane-associated glycoproteins. However, two regions of substantial divergence were noted, one spanning the origin of replication and the other encoding one of the putative HHV-6-specific glycoprotein genes. Substitutions in the latter region lead to predicted differences in reading frames and protein lengths among HHV-6 isolates.

Comparison of a 20 kb region of human herpesvirus 6B with other human beta herpesviruses reveals conserved replication genes and adjacent divergent open reading frames.

The sequence of a 20.15 kb region from human herpesvirus 6 variant B (HHV-6B) strain Z29 is described (GenBank accession number L14772). Determinations of protein homologies for seventeen predicted gene products revealed HHV-6B homologs of six proteins well-conserved both in genetic context and amino acid sequence throughout the alpha-, beta-, and gammaherpesvirus subfamilies. These include proteins involved in viral DNA replication, packaging and nucleotide metabolism, and conserved proteins of undefined function. The close evolutionary relationship of the human betaherpesviruses, HHV-6B, HHV-6A, HHV-7 and human cytomegalovirus (HCMV) was confirmed by identification of several protein sequences encoded only by these viruses, including homologs of the HCMV early phosphoprotein family and a series of HCMV open reading frames predicted to encode glycoprotein exons. Homologs of essential HSV-1 replication proteins, UL8 and UL9, were also identified. Downstream from the conserved replication locus, each betaherpesvirus contains a region of divergent, small open reading frames. The evolution of this region and its potential use in the development of a viral vector system are discussed.