{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T20:54:18Z","timestamp":1774385658755,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009720","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000}}],"reference-count":109,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"Chinese Scholarship Council","doi-asserted-by":"crossref","award":["201706620069"],"award-info":[{"award-number":["201706620069"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_1201412"],"award-info":[{"award-number":["MC_UU_1201412"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Human immunodeficiency virus type 1 (HIV-1) continues to be a major cause of disease and premature death. As with all viruses, HIV-1 exploits a host cell to replicate. Improving our understanding of the molecular interactions between virus and human host proteins is crucial for a mechanistic understanding of virus biology, infection and host antiviral activities. This knowledge will potentially permit the identification of host molecules for targeting by drugs with antiviral properties. Here, we propose a data-driven approach for the analysis and prediction of the HIV-1 interacting proteins (VIPs) with a focus on the directionality of the interaction: host-dependency versus antiviral factors. Using support vector machine learning models and features encompassing genetic, proteomic and network properties, our results reveal some significant differences between the VIPs and non-HIV-1 interacting human proteins (non-VIPs). As assessed by comparison with the HIV-1 infection pathway data in the Reactome database (sensitivity &gt; 90%, threshold = 0.5), we demonstrate these models have good generalization properties. We find that the \u2018direction\u2019 of the HIV-1-host molecular interactions is also predictable due to different characteristics of \u2018forward\u2019\/pro-viral versus \u2018backward\u2019\/pro-host proteins. Additionally, we infer the previously unknown direction of the interactions between HIV-1 and 1351 human host proteins. A web server for performing predictions is available at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/hivpre.cvr.gla.ac.uk\/\" xlink:type=\"simple\">http:\/\/hivpre.cvr.gla.ac.uk\/<\/jats:ext-link>.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009720","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T18:33:29Z","timestamp":1644345209000},"page":"e1009720","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["In silico prediction of HIV-1-host molecular interactions and their directionality"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0558-3965","authenticated-orcid":true,"given":"Haiting","family":"Chai","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-6734","authenticated-orcid":true,"given":"Quan","family":"Gu","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2556-2563","authenticated-orcid":true,"given":"Joseph","family":"Hughes","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6338-0221","authenticated-orcid":true,"given":"David L.","family":"Robertson","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"issue":"12","key":"pcbi.1009720.ref001","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.tim.2015.09.003","article-title":"The HIV-1 entry process: a stoichiometric view","volume":"23","author":"OF Brandenberg","year":"2015","journal-title":"Trends Microbiol"},{"issue":"2","key":"pcbi.1009720.ref002","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nrmicro.2016.162","article-title":"Nuclear landscape of HIV-1 infection and integration","volume":"15","author":"M Lusic","year":"2017","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"pcbi.1009720.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nrdp.2015.35","article-title":"HIV infection.","volume":"1","author":"SG Deeks","year":"2015","journal-title":"Nature reviews Disease primers"},{"issue":"1","key":"pcbi.1009720.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-4690-4-36","article-title":"A real-time view of the TAR: Tat: P-TEFb complex at HIV-1 transcription sites.","volume":"4","author":"D Molle","year":"2007","journal-title":"Retrovirology"},{"issue":"3","key":"pcbi.1009720.ref005","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1600-0854.2011.01286.x","article-title":"The ins and outs of HIV-1","volume":"13","author":"S Debaisieux","year":"2012","journal-title":"Tat. 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