Infectivity determinants encoded in a conserved gene block of human herpesvirus-6

Abstract

The nucleotide sequence was determined for a 9.3 kb BamHI DNA fragment derived from a cosmid clone (Lorist 6) library of the 160 kb human herpesvirus-6 (HHV-6) strain U1102 genome. Analysis of the sequence showed two different sources for the DNA; 8.0 kb was derived from HHV-6, while 1.3 kb was derived from the right repeat of transposon Tn10, the insertion sequence (IS) element IS10R. The IS element sequence is shown to be derived from the host bacteria of the plasmid. The HHV-6 sequence represents a highly conserved part of the genome encoding 15% of the genes conserved among the other human herpesviruses in only 5% of the genome. Six genes were identified, five encoding products with amino acid sequence similarity to homologues in herpes simplex virus (HSV), Varicella Zoster Virus (VZV), human cytomegalovirus (CMV) and Epstein-Barr Virus (EBV). All had closest amino acid similarity to CMV proteins. Three clustered structural genes, included glycoprotein H, a major conserved determinant of infectivity, were jointed to a putative dUTPase homologue in an arrangement distinct to CMV and HHV-6. In the other herpes viruses these genes are separated by over 50 kb. The gene at this point of genetic rearrangement had no sequence similarity to proteins of other herpesviruses. However, there is a protein at this locus in CMV with similar composition and character. Both appear to be highly glycosylated, secreted glycoproteins with repetitive elements similar to those of human mucins. Comparison of sequence available in the HHV-6 GS strain also shows this to be a variable region (5% nucleotide differences) in an overall conserved DNA sequence (0.5%).