Analysis of the human herpesvirus-6 immediate-early 1 protein.
Herpesvirus immediate-early (IE) gene products play key roles in establishing productive infections, regulating reactivation from latency and evading immune recognition. Analyses of HHV-6 IE gene expression have revealed that the IE1 gene of the HHV-6A and HHV-6B variants exhibits a higher degree of sequence variation than other regions of the genome and no obvious similarity to its positional analogue in HCMV. We have analysed expression of the HHV-6 U1102 (HHV-6A) and Z29 (HHV-6B) IE1 gene products using transient expression vectors, stable cell lines and in the context of lytic virus infection. The IE1 transcripts from both variants demonstrate a similar pattern of splice usage within their translated regions. The HHV-6 IE1 proteins from both variants traffic to, and form a stable interaction with, PML-bodies (also known as ND10 or PODS). Remarkably, PML-bodies remained structurally intact and associated with the IE1 protein throughout lytic HHV-6 infection. Immunoprecipitation studies demonstrated that HHV-6 IE1 from both variants is covalently modified by conjugation to the small ubiquitin-like protein SUMO-1. Overexpression of SUMO-1 in cell lines resulted in substantially enhanced levels of IE1 expression; thus sumoylation may bestow stability to the protein. These results indicate that the HHV-6 IE1 protein interacts with PML-bodies yet, unlike other herpesviruses, HHV-6 appears to have no requirement or mechanism to induce PML-body dispersal during lytic replication.
Stanton
Richard
R
Department of Medical Microbiology1 and Section of Infection and Immunity2, University of Wales College of Medicine, Tenovus Building, Heath Park, Cardiff CF14 4XN, UK.
Fox
Julie D
JD
Department of Medical Microbiology1 and Section of Infection and Immunity2, University of Wales College of Medicine, Tenovus Building, Heath Park, Cardiff CF14 4XN, UK.
Caswell
Richard
R
Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, UK3.
Sherratt
Emma
E
Department of Medical Microbiology1 and Section of Infection and Immunity2, University of Wales College of Medicine, Tenovus Building, Heath Park, Cardiff CF14 4XN, UK.
Wilkinson
Gavin W G
GWG
Department of Medical Microbiology1 and Section of Infection and Immunity2, University of Wales College of Medicine, Tenovus Building, Heath Park, Cardiff CF14 4XN, UK.
D002478:Cells, Cultured; D015654:Herpesvirus 6, Human / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D025842:SUMO-1 Protein; C458509:immediate-early 1 protein, human herpesvirus 6