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

Virology. 1994 Oct;204(1):304-11. doi: 10.1006/viro.1994.1535.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DNA Replication*
  • DNA, Viral / biosynthesis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Dependovirus / growth & development*
  • Gene Expression Regulation, Viral / genetics*
  • Genes, Regulator / physiology
  • Genes, Viral / physiology
  • Genetic Complementation Test
  • HIV Long Terminal Repeat / genetics
  • Helper Viruses / physiology*
  • Herpesvirus 6, Human / physiology*
  • Humans
  • Recombinant Fusion Proteins / biosynthesis
  • Sequence Deletion / physiology
  • Sequence Homology, Nucleic Acid
  • Transcriptional Activation
  • Transfection
  • Viral Proteins / genetics*
  • Viral Proteins / physiology
  • Virus Replication / genetics*


  • DNA, Viral
  • DNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Viral Proteins
  • rep proteins, Adeno-associated virus 2

Associated data

  • GENBANK/X83413