In silico prediction of HIV-1-host molecular interactions and their directionality.

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 underst...

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Main Authors: Haiting Chai, Quan Gu, Joseph Hughes, David L Robertson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-02-01
Series:PLoS Computational Biology
Online Access:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009720&type=printable
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author Haiting Chai
Quan Gu
Joseph Hughes
David L Robertson
author_facet Haiting Chai
Quan Gu
Joseph Hughes
David L Robertson
author_sort Haiting Chai
collection DOAJ
description 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 > 90%, threshold = 0.5), we demonstrate these models have good generalization properties. We find that the 'direction' of the HIV-1-host molecular interactions is also predictable due to different characteristics of 'forward'/pro-viral versus 'backward'/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 http://hivpre.cvr.gla.ac.uk/.
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spelling doaj-art-9c3c63d712434eb9a6b1a026b6ebd6012025-08-20T02:23:18ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582022-02-01182e100972010.1371/journal.pcbi.1009720In silico prediction of HIV-1-host molecular interactions and their directionality.Haiting ChaiQuan GuJoseph HughesDavid L RobertsonHuman 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 > 90%, threshold = 0.5), we demonstrate these models have good generalization properties. We find that the 'direction' of the HIV-1-host molecular interactions is also predictable due to different characteristics of 'forward'/pro-viral versus 'backward'/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 http://hivpre.cvr.gla.ac.uk/.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009720&type=printable
spellingShingle Haiting Chai
Quan Gu
Joseph Hughes
David L Robertson
In silico prediction of HIV-1-host molecular interactions and their directionality.
PLoS Computational Biology
title In silico prediction of HIV-1-host molecular interactions and their directionality.
title_full In silico prediction of HIV-1-host molecular interactions and their directionality.
title_fullStr In silico prediction of HIV-1-host molecular interactions and their directionality.
title_full_unstemmed In silico prediction of HIV-1-host molecular interactions and their directionality.
title_short In silico prediction of HIV-1-host molecular interactions and their directionality.
title_sort in silico prediction of hiv 1 host molecular interactions and their directionality
url https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009720&type=printable
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