Positive and negative autoregulation of the adeno-associated virus type 2 genome.
AUTOR(ES)
Labow, M A
RESUMO
The defective human parvovirus, adeno-associated virus (AAV), requires multiple functions provided by a coinfecting helper virus for viral replication. In addition, it has recently been shown that at least one AAV gene is also required for AAV DNA replication. In this paper, we investigate the autoregulation of the AAV genome by analyzing the expression of mutant AAV genomes upon transfection into adenovirus-infected human cells. Evidence is presented which indicates that the AAV genome regulates its own gene expression in at least two ways. First, either the AAV p5 gene or both the p5 and p19 genes appear to encode a trans activator of AAV transcription. Frameshift mutations within the p5 or p19 gene severely inhibited the synthesis and accumulation of all AAV transcripts. The defective accumulation of transcripts could be complemented in trans, in a manner independent of DNA replication, by cotransfection with a capsid deletion mutant. Second, evidence is presented which suggests that the p5 and p19 genes contain negative cis-active regulatory elements. Deletion of sequences within the p5 and p19 genes enhanced the accumulation of the p5 transcript in cis upon complementation with an AAV capsid deletion mutant, whereas certain deletions enhanced p40 RNA accumulation in the absence of trans activation by the p5 gene.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=253923Documentos Relacionados
- Nucleotide sequence and organization of the adeno-associated virus 2 genome.
- A novel terminal resolution-like site in the adeno-associated virus type 2 genome.
- Genetics of adeno-associated virus: isolation and preliminary characterization of adeno-associated virus type 2 mutants.
- Binding sites for adeno-associated virus Rep proteins within the human genome.
- Genome localization of adeno-associated virus RNA.