Transcriptional analysis of the adeno-associated virus integration site.

N. Dutheil, E. Henckaerts, E. Kohlbrenner, R. M. Linden
Journal of Virology. 2009-09-16; 83(23): 12512-12525
DOI: 10.1128/jvi.01754-09

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1. J Virol. 2009 Dec;83(23):12512-25. doi: 10.1128/JVI.01754-09. Epub 2009 Sep 16.

Transcriptional analysis of the adeno-associated virus integration site.

Dutheil N(1), Henckaerts E, Kohlbrenner E, Linden RM.

Author information:
(1)Department of Infectious Diseases, King’s College London School of Medicine,
London SE1 9RT, United Kingdom.

The nonpathogenic human adeno-associated virus type 2 (AAV-2) has adopted a
unique mechanism to site-specifically integrate its genome into the human MBS85
gene, which is embedded in AAVS1 on chromosome 19. The fact that AAV has evolved
to integrate into this ubiquitously transcribed region and that the chromosomal
motifs required for integration are located a few nucleotides upstream of the
translation initiation start codon of MBS85 suggests that the transcriptional
activity of MBS85 might influence site-specific integration and thus might be
involved in the evolution of this mechanism. In order to begin addressing this
question, we initiated the characterization of the human MBS85 promoter region
and compared its transcriptional activity to that of the AAV-2 p5 promoter. Our
results clearly indicate that AAVS1 is defined by a complex transcriptional
environment and that the MBS85 promoter shares key regulatory elements with the
viral p5 promoter. Furthermore, we provide evidence for bidirectional MBS85
promoter activity and demonstrate that the minimal motifs required for AAV
site-specific integration are present in the 5′ untranslated region of the gene
and play a posttranscriptional role in the regulation of MBS85 expression. These
findings should provide a framework to further elucidate the complex interactions
between the virus and its cellular host in this unique pathway to latency.

DOI: 10.1128/JVI.01754-09
PMCID: PMC2786763
PMID: 19759129 [Indexed for MEDLINE]

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