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

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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.

Original languageEnglish
Article numbere7825
JournalPloS one
Volume4
Issue number11
DOIs
Publication statusPublished - 13-11-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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