Human herpesvirus 6 (HHV-6) is a helper virus for adeno-associated virus type 2 (AAV-2) and the AAV-2 rep gene homologue in HHV-6 can mediate AAV-2 DNA replication and regulate gene expression.
We have previously described the apparent acquisition by human herpesvirus 6 (HHV-6) of the multifunctional rep gene of the helper-dependent human parvovirus adeno-associated virus type 2 (AAV-2). We report here 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 recombination of replicative intermediates. The HHV-6 rep gene cloned under control of the human cytomegalovirus immediate early promoter complemented replication of a rep-deficient AAV-2 genome. In cotransfection experiments with heterologous promoters linked to the CAT reporter gene, HHV-6 rep activated the human immunodeficiency virus (HIV) long terminal repeat (LTR) in fibroblast cell lines but not in T-cells. In contrast, 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 was independent of the NF-kappa B, Sp1, and TATA box elements. These results suggest that HHV-6 Rep is a multifunctional regulatory protein with properties related to, but distinct from, those of AAV-2 Rep.
Thomson
B J
BJ
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, UK.
Weindler
F W
FW
Gray
D
D
Schwaab
V
V
Heilbronn
R
R
D002460:Cell Line; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D000229:Dependovirus / Q000254:growth & development*; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D005809:Genes, Regulator / Q000502:physiology; D005814:Genes, Viral / Q000502:physiology; D005816:Genetic Complementation Test; D016325:HIV Long Terminal Repeat / Q000235:genetics; D006378:Helper Viruses / Q000502:physiology*; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017384:Sequence Deletion / Q000502:physiology; D012689:Sequence Homology, Nucleic Acid; D015533:Transcriptional Activation; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics* / Q000502:physiology; D014779:Virus Replication / Q000235:genetics*
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C068734:rep proteins, Adeno-associated virus 2