The sequence of 10079 bp corresponding to the overlapping I H and I G restriction fragments of the genome of human herpesvirus 6 (HHV-6) strain U1102 was determined. The sequence contains six complete open reading frames (ORFs) and two incomplete ORFs located at the 5′ and 3′ ends of the I H and I G fragments respectively. Seven of these ORFs have recognizable homologues only in the betaherpesvirus human cytomegalovirus (HCMV), no obvious counterparts being detectable in the genomes of the human alphaherpesviruses, varicella-zoster virus and herpes simplex virus type 1 or the gammaherpesvirus Epstein-Barr virus. The DNA sequenced is located proximal to the left repeat of the HHV-6 genome outside the well recognized region encompassing conserved herpesvirus gene blocks. A close collinear relationship is evident between the HHV-6 ORFs identified in this study and their counterparts in HCMV, ORFs UL23, UL24 and UL27 to UL31. Four of the HHV-6 ORFs, SHL1, SHL2, SFL1 and SSL2, are related to members of the HCMV US22 family of proteins, which are themselves tandemly arranged and located predominantly within the unique short and the left end of the unique long region of the prototype HCMV strain AD169 genome. Two adjacent HHV-6 ORFs, SSL1 and SHL3, are related to HCMV UL27. The identification of this gene set in addition to the HHV-6 ORFs with amino acid sequence similarity to the HCMV US22 family indicates a particularly close relationship between these two human herpesviruses, and suggests that the clustering of these related tandemly arranged genes may be a general feature of betaherpesvirus-type genomes.


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