title: Analysis of human herpesvirus-6 IE1 sequence variation in clinical samples.
abstract: Herpesvirus immediate early (IE) proteins are known to play key roles in establishing productive infections, regulating reactivation from latency, and creating a cellular environment favourable to viral replication. Human herpesvirus-6 (HHV-6) IE genes have not been studied as intensively as their homologues in the prototype betaherpesvirus human cytomegalovirus (HCMV). Whilst the HCMV IE1 gene is relatively conserved, early studies indicated that HHV-6 IE1 exhibited a high level of sequence variation between HHV-6A and HHV-6B isolates, although the observation was based primarily on virus stocks that had been isolated and propagated in vitro. In this study, we investigated the level of HHV-6 IE1 sequence variation in vivo by direct sequencing of circulating virus in clinical samples without prior in vitro culture. Sequences exactly matching those reported for reference HHV-6 isolates were identified in clinical samples, thus the HHV-6 laboratory strains used in the majority of in vitro studies appear to be representative of virus circulating in vivo with respect to the IE1 gene. The HHV-6 IE1 sequence is also conserved in reference strains that had been passaged extensively in vitro. The high degree of divergence between variant A and B type IE1 sequences was confirmed, but interestingly HHV-6B IE1 sequences were observed to further segregate into two distinct subgroups, with the laboratory strains Z29 and HST representative of these two subgroups. Within each HHV-6B subgroup, a remarkably high level of homology was observed. Thus the HHV-6 IE1 sequence appears highly stable, underlining its potential importance to the viral life cycle.
authors.affiliation: Department of Medical Microbiology, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom. richstanton@bigfoot.com
authors.forename: Richard
authors.initials: R
authors.lastname: Stanton
authors.forename: Gavin W G
authors.initials: GW
authors.lastname: Wilkinson
authors.forename: Julie D
authors.initials: JD
authors.lastname: Fox
mesh_terms: D000328:Adult; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D002648:Child; D004279:DNA, Viral / Q000235:genetics; D014644:Genetic Variation; D015654:Herpesvirus 6, Human / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D016867:Immunocompromised Host; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010750:Phosphoproteins / Q000235:genetics*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D019349:Roseolovirus Infections / Q000821:virology*
chemical_list: D004279:DNA, Viral; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; C458509:immediate-early 1 protein, human herpesvirus 6