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Journal of Virology, February 2007, p. 1990-2001, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.02014-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Adeno-Associated Virus Site-Specific Integration Is Regulated by TRP-185{triangledown}

Noriaki Yamamoto,1 Masato Suzuki,1 Masa-aki Kawano,1 Takamasa Inoue,1 Ryou-u Takahashi,1 Hiroko Tsukamoto,1 Teruya Enomoto,1 Yuki Yamaguchi,1 Tadashi Wada,2 and Hiroshi Handa1*

Graduate School of Bioscience and Biotechnology,1 Integrated Research Institute, Tokyo Institute of Technology, Yokohama, Kanagawa 226-8501, Japan2

Received 15 September 2006/ Accepted 25 November 2006

Adeno-associated virus (AAV) integrates site specifically into the AAVS1 locus on human chromosome 19. Although recruitment of the AAV nonstructural protein Rep78/68 to the Rep binding site (RBS) on AAVS1 is thought to be an essential step, the mechanism of the site-specific integration, particularly, how the site of integration is determined, remains largely unknown. Here we describe the identification and characterization of a new cellular regulator of AAV site-specific integration. TAR RNA loop binding protein 185 (TRP-185), previously reported to associate with human immunodeficiency virus type 1 TAR RNA, binds to AAVS1 DNA. Our data suggest that TRP-185 suppresses AAV integration at the AAVS1 RBS and enhances AAV integration into a region downstream of the RBS. TRP-185 bound to Rep68 directly, changing the Rep68 DNA binding property and stimulating Rep68 helicase activity. We present a model in which TRP-185 changes the specificity of the AAV integration site from the RBS to a downstream region by acting as a molecular chaperone that promotes Rep68 complex formation competent for 3'->5' DNA helicase activity.

* Corresponding author. Mailing address: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan. Phone: 81-45-924-5872. Fax: 81-45-924-5145. E-mail: hhanda{at}bio.titech.ac.jp.

{triangledown} Published ahead of print on 6 December 2006.

Journal of Virology, February 2007, p. 1990-2001, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.02014-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nash, K., Chen, W., Salganik, M., Muzyczka, N. (2009). Identification of Cellular Proteins That Interact with the Adeno-Associated Virus Rep Protein. J. Virol. 83: 454-469 [Abstract] [Full Text]  
  • Daya, S., Berns, K. I. (2008). Gene Therapy Using Adeno-Associated Virus Vectors. Clin. Microbiol. Rev. 21: 583-593 [Abstract] [Full Text]  


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