Global analysis of host-pathogen interactions that regulate early stage HIV-1 replication

By Renate König, Yingyao Zhou, D. Elleder, Tracy L. Diamond, G. Bonamy, J. Irelan, Chih-yuan Chiang, Buu Tu, Paul D. De Jesus, C. Lilley and 12 more. Cell, 2008

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Human Immunodeficiency Viruses (HIV-1 and HIV-2) rely upon host-encoded proteins to facilitate their replication. Here we combined genome-wide siRNA analyses with interrogation of human interactome databases to assemble a host-pathogen biochemical network containing 213 confirmed host cellular factors and 11 HIV-1-encoded proteins. Protein complexes that regulate ubiquitin conjugation, proteolysis, DNA damage response and RNA splicing were identified as important modulators of early stage HIV-1 infection. Additionally, over 40 new factors were shown to specifically influence initiation and/or kinetics of HIV-1 DNA synthesis, including cytoskeletal regulatory proteins, modulators of post-translational modification, and nucleic acid binding proteins. Finally, fifteen proteins with diverse functional roles, including nuclear transport, prostaglandin synthesis, ubiquitination, and transcription, were found to influence nuclear import or viral DNA integration. Taken together, the multi-scale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate early steps of HIV-1 infection.

Subfields: Infectious Diseases, Molecular Biology, Virology

View Paper: https://www.semanticscholar.org/paper/58675c5ff457ad5640440ba92404029170dd2380

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In Infectious Diseases

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  4. Jason Aaron Edward Weston
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  8. Ryan D. Hernandez

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