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Transcription Factor YY1 Interacts with Retroviral Integrases and Facilitates Integration of Moloney Murine Leukemia Virus cDNA into the Host Chromosomes

2010; American Society for Microbiology; Volume: 84; Issue: 16 Linguagem: Inglês

10.1128/jvi.02681-09

1098-5514

Yujin Inayoshi, Yuuki Okino, Katsuhide Miyake, Akifumi Mizutani, Junko Yamamoto-Kishikawa, Yuya Kinoshita, Yusuke V. Morimoto, Kazuhito Imamura, Mahboob Morshed, Ken Kono, Toshinari Itoh, Ken‐ichi Nishijima, Shinji Iijima,

Virus-based gene therapy research

ABSTRACT Retroviral integrases associate during the early viral life cycle with preintegration complexes that catalyze the integration of reverse-transcribed viral cDNA into the host chromosomes. Several cellular and viral proteins have been reported to be incorporated in the preintegration complex. This study demonstrates that transcription factor Yin Yang 1 binds to Moloney murine leukemia virus, human immunodeficiency virus type 1, and avian sarcoma virus integrases. The results of coimmunoprecipitation and in vitro pulldown assays revealed that Yin Yang 1 interacted with the catalytic core and C-terminal domains of Moloney murine leukemia virus and human immunodeficiency virus type 1 integrases, while the transcriptional repression and DNA-binding domains of the Yin Yang 1 molecule interacted with Moloney murine leukemia virus integrase. Immunoprecipitation of the cytoplasmic fraction of virus-infected cells followed by Southern blotting and chromatin immunoprecipitation demonstrated that Yin Yang 1 associated with Moloney murine leukemia virus cDNA in virus-infected cells. Yin Yang 1 enhanced the in vitro integrase activity of Moloney murine leukemia virus, human immunodeficiency virus type 1, and avian sarcoma virus integrases. Furthermore, knockdown of Yin Yang 1 in host cells by small interfering RNA reduced Moloney murine leukemia virus cDNA integration in vivo , although viral cDNA synthesis was increased, suggesting that Yin Yang 1 facilitates integration events in vivo . Taking these results together, Yin Yang 1 appears to be involved in integration events during the early viral life cycle, possibly as an enhancer of integration.