augmentation of reverse transcription by integrase through an interaction with host factor, sip1gemin2 is critical for hiv-1 infection增加的逆转录通过与主机的交互因素整合酶,sip1gemin2对hiv - 1感染至关重要.pdf

Augmentation of Reverse Transcription by Integrase through an Interaction with Host Factor, SIP1/Gemin2 Is Critical for HIV-1 Infection ¤ Hironori Nishitsuji , Takaya Hayashi, Takuya Takahashi, Masashi Miyano, Mari Kannagi, Takao Masuda* Department of Immunotherapeutics, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan Abstract There has been accumulating evidence for the involvement of retroviral integrase (IN) in the reverse transcription of viral RNA. We previously identified a host factor, survival motor neuron-interacting protein 1 (SIP1/Gemin2) that binds to human immunodeficiency virus type 1 (HIV-1) IN and supports HIV-1 infection apparently at reverse transcription step. Here, we demonstrated that HIV-1 IN together with SIP1 augments reverse transcriptase (RT) activity by enhancing the assembly of RT on viral RNA in vitro. Synthetic peptides corresponding to the binding motifs within IN that inhibited the IN-SIP1 interaction abrogated reverse transcription in vitro and in vivo. Furthermore, knockdown of SIP1 reduced intracellular stability and multimer formation of IN through proteasome-mediated degradation machinery. Taken together, SIP1 appears to stabilize functional multimer forms of IN, thereby promoting the assembly of IN and RT on viral RNA to allow efficient reverse transcription, which is a prerequisite for efficient HIV-1 infection. Citation: Nishitsuji H, Hayashi T, Takahashi T, Miyano M, Kannagi M, et al. (2009) Augmentation of Reverse Transcription by Integrase through an Interaction with Host Factor, SIP1/Gemin2 Is Critical for HIV-1 Infection. PLoS ONE 4(11): e7825. doi:10.1371/journal.pone.0007825 Editor: Wang-Shick Ryu, Yonsei University, Republic of Korea Received September 2, 2009; Accepted October 16, 2009; Published November 13, 2009 Copyright: 2