Analysis of the human herpesvirus-6 immediate-early 1 protein

J Gen Virol. 2002 Nov;83(Pt 11):2811-2820. doi: 10.1099/0022-1317-83-11-2811.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Herpesvirus 6, Human / metabolism*
  • Herpesvirus 6, Human / physiology
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • SUMO-1 Protein / metabolism
  • Tumor Cells, Cultured


  • Immediate-Early Proteins
  • Phosphoproteins
  • SUMO-1 Protein
  • immediate-early 1 protein, human herpesvirus 6