Relationship between U83 gene variation in human herpesvirus 6 and secretion of the U83 gene product

The betaherpesvirus human herpesvirus 6 (HHV-6) has two variants. The U83 gene product of strain HST is a chemoattractant for monocytes. Here, we describe U83 gene variations that accumulated in variants A and B. A gene-variation hot spot was examined in 36 different strains and one donor DNA sample. U83 gene variations accumulated in variant A and in reactivated variant B after transplantation. None of the variant-A viruses encoded the signal peptide found in the B variant. U83 gene sequencing suggested that the variant A and B groups were separate, and that the variant B viruses could be further divided into the HST-Z29 type and another type with a shorter signal peptide. In a eukaryotic expression system, the HST-Z29 type of U83 gene product was secreted into the medium, a frame-shifted HST-Z29 type was partially secreted, and the variant-A type and a first-methionine knockout of the HST-Z29 type were not secreted.