HUMAN HERPESVIRUS-6 (HHV-6) IS A HELPER VIRUS FOR ADENOASSOCIATED VIRUS TYPE-2 (AAV-2) AND THE AAV-2 REP GENE HOMOLOG IN HHV-6 CAN MEDIATE AAV-2 DNA-REPLICATION AND REGULATE GENE-EXPRESSION

We have previously described the apparent acquisition by human herpesv irus 6 (HHV-6) of the multifunctional rep gene of the helper-dependent human parvovirus adeno-associated virus type 2 (AAV-2). We report her e that HHV-6 is a full helper virus for AAV-2 replication, suggesting a mechanism for transfer of the rep gene between the two viruses by re combination of replicative intermediates. The HHV-6 rep gene cloned un der control of the human cytomegalovirus immediate early promoter comp lemented replication of a rep-deficient AAV-2 genome. In cotransfectio n experiments with heterologous promoters linked to the CAT reporter g ene, HHV-6 rep activated the human immunodeficiency virus (HIV) long t erminal repeat (LTR) in fibroblast cell lines but not in T-cells. In c ontrast, AAV-2 rep inhibited HIV LTR activity in both fibroblast and T -cell lines, The effect of HHV-6 and AAV-2 rep genes on the HIV LTR wa s independent of the NF-kappa B, Sp1, and TATA box elements. These res ults suggest that HHV-6 Rep is a multifunctional regulatory protein wi th properties related to, but distinct from, those of AAV-2 Rep. (C) 1 994 Academic Press, Inc.