Proteins of HHV-6

Abstract

Publisher Summary Human herpesvirus-6 (HHV-6) is classified into variants A (HHV-6A) and B (HHV-6B) on the basis of distinct genetic, immunological, and biological characteristics. The HHV-6 genome contains open reading frames (ORFs) U1-U100 and flanking 8–9 kb terminal direct repeats (DRs) at either end. HHV-6B contains 119 ORFs and HHV-6A contains 110 ORFs. HHV-6 gene transcription follows a similar pattern that characterizes herpesvirus, with immediate-early (IE), early and late proteins expressed. HHV-6 immediate-early A locus (IE-A) locates in the position analogous to the human cytomegalovirus (HCMV) major IE (MIE) locus that is well-known to play critical roles in viral infection. Similarly to HCMV MIE, HHV-6 IE-A consists of two genetic units, IE1 and IE2, corresponding to ORFs U90–U89 and U90–U86/87, respectively. However, the HHV-6 IE-A locus exhibits limited sequence homology with the HCMV MIE locus. The U17/ U16 and the U16+ gene products transactivate the HIV LTR. Thus, while there are similarities to the HCMV UL36–UL38 gene family, some of the IE-B U17/U16 transcripts are unique to HHV-6. HHV-6 U53 encodes its own proteinase, which is essential for capsid maturation, DNA packaging and the ultimate formation of new virus particles. HHV-6 U69 gene product (pU69) is the presumed functional homologue of HCMV UL97-encoded kinase (pUL97), which converts ganciclovir into its monophosphate metabolite in HCMV-infected cells. The U94 transcript is spliced to remove a 2.6-kb intron and is expressed at very low levels relative to other HHV-6B genes, reaching approximately 10 copies/cell three days after infection.