Identification of a novel human immunodeficiency virus type 1 integrase interactor, Gemin2, that facilitates efficient viral cDNA synthesis in vivo.

Abstract

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.

• Authors: Seiji Hamamoto, Hironori Nishitsuji, Teruo Amagasa, Mari Kannagi, Takao Masuda
• Journal: Journal of virology (J Virol) Vol. 80 Issue 12 Pg. 5670-7 (Jun 2006) ISSN: 0022-538X [Print] United States
• PMID: 16731905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• GEMIN2 protein, human
• Nerve Tissue Proteins
• RNA-Binding Proteins
• Retroviridae Proteins
• HIV Integrase

Topics

• Cells, Cultured
• DNA, Complementary (biosynthesis)
• HIV Integrase (metabolism)
• HIV-1 (enzymology, physiology)
• Humans
• Macrophages (virology)
• Nerve Tissue Proteins (metabolism, physiology)
• Protein Binding
• RNA-Binding Proteins (metabolism, physiology)
• Retroviridae Proteins (metabolism)
• Two-Hybrid System Techniques
• Virus Integration