Augmentation of reverse transcription by integrase through an interaction with host factor, SIP1/Gemin2 Is critical for HIV-1 infection.

Full 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.

Author information

Author/s: Nishitsuji, Hironori (H); Hayashi, Takaya (T); Takahashi, Takuya (T); Miyano, Masashi (M); Kannagi, Mari (M); Masuda, Takao (T);

Affiliation: Department of Immunotherapeutics, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: PloS one (PLoS One), published in United States. (Language: eng)

Reference: 2009-; vol 4 (issue 11) : pp e7825

Dates: Created 2009/11/16;

PMID: 19915660, status: In-Process (last retrieved date: 11/23/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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