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Journal of Virology, June 2006, p. 5670-5677, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02471-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Identification of a Novel Human Immunodeficiency Virus Type 1 Integrase Interactor, Gemin2, That Facilitates Efficient Viral cDNA Synthesis In Vivo

Seiji Hamamoto,1,2,{dagger} Hironori Nishitsuji,1,{dagger} Teruo Amagasa,2 Mari Kannagi,1 and Takao Masuda1*

Department of Immunotherapeutics, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan,1 Department of Maxillofacial Surgery, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan2

Received 23 November 2005/ Accepted 27 March 2006

Retroviral integrase (IN) catalyzes the integration of viral cDNA into a host chromosome. Additional roles have been suggested for IN, including uncoating, reverse transcription, and nuclear import of the human immunodeficiency virus type 1 (HIV-1) genome. However, the underlying mechanism is largely unknown. Here, using a yeast two-hybrid system, we identified a survival motor neuron (SMN)-interacting protein 1 (Gemin2) that binds to HIV-1 IN. Reduction of Gemin2 with small interfering RNA duplexes (siGemin2) dramatically reduced HIV-1 infection in human primary monocyte-derived macrophages and also reduced viral cDNA synthesis. In contrast, siGemin2 did not affect HIV-1 expression from the integrated proviral DNA. Although Gemin2 was undetectable in cell-free viral particles, coimmunoprecipitation experiments using FLAG-tagged Gemin2 strongly suggested that Gemin2 interacts with the incoming viral genome through IN. Further experiments reducing SMN or other SMN-interacting proteins suggested that Gemin2 might act on HIV-1 either alone or with unknown proteins to facilitate efficient viral cDNA synthesis soon after infection. Thus, we provide the evidence for a novel host protein that binds to HIV-1 IN and facilitates viral cDNA synthesis and subsequent steps that precede integration in vivo.

* Corresponding author. Mailing address: Department of Immunotherapeutics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Phone: 81-3-5803-5799. Fax: 81-3-5803-0235. E-mail: tmasu.impt{at}tmd.ac.jp.

{dagger} S.H. and H.N. contributed equally to this work.

Journal of Virology, June 2006, p. 5670-5677, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02471-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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