Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents

RNAi screens have implicated hundreds of host proteins as HIV-1 dependency factors (HDFs). While informative, these early studies overlap poorly due to false positives and false negatives. To ameliorate these issues, we combined information from the existing HDF screens together with new screens per...

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Main Authors:	Zhu, Jian, Davoli, Teresa, Perriera, Jill M., Chin, Christopher R., Gaiha, Gaurav D., John, Sinu P., Sigiollot, Frederic D., Gao, Geng, Xu, Qikai, Qu, Hongjing, Pertel, Thomas, Sims, Jennifer S., Smith, Jennifer A., Baker, Richard E., Maranda, Louise, Ng, Aylwin, Elledge, Stephen J., Brass, Abraham L.
Format:	Online
Language:	English
Published:	2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926641/

id	pubmed-4926641
recordtype	oai_dc
spelling	pubmed-49266412016-06-29 Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents Zhu, Jian Davoli, Teresa Perriera, Jill M. Chin, Christopher R. Gaiha, Gaurav D. John, Sinu P. Sigiollot, Frederic D. Gao, Geng Xu, Qikai Qu, Hongjing Pertel, Thomas Sims, Jennifer S. Smith, Jennifer A. Baker, Richard E. Maranda, Louise Ng, Aylwin Elledge, Stephen J. Brass, Abraham L. Article RNAi screens have implicated hundreds of host proteins as HIV-1 dependency factors (HDFs). While informative, these early studies overlap poorly due to false positives and false negatives. To ameliorate these issues, we combined information from the existing HDF screens together with new screens performed with multiple orthologous RNAi reagents (MORR). In addition to being traditionally validated, the MORR screens and the historical HDF screens were quantitatively integrated by the adaptation of an established analysis program, RIGER, for the collective interpretation of each gene’s phenotypic significance. False positives were addressed by the removal of poorly expressed candidates through gene expression filtering, as well as with GESS, which identifies off-target effects. This workflow produced a quantitatively integrated network of genes that modulate HIV-1 replication. We further investigated the roles of GOLGI49, SEC13, and COG in HIV-1 replication. Collectively, the MORR-RIGER method minimized the caveats of RNAi screening and improved our understanding of HIV-1–host cell interactions. 2014-10-16 2014-10-23 /pmc/articles/PMC4926641/ /pubmed/25373910 http://dx.doi.org/10.1016/j.celrep.2014.09.031 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhu, Jian Davoli, Teresa Perriera, Jill M. Chin, Christopher R. Gaiha, Gaurav D. John, Sinu P. Sigiollot, Frederic D. Gao, Geng Xu, Qikai Qu, Hongjing Pertel, Thomas Sims, Jennifer S. Smith, Jennifer A. Baker, Richard E. Maranda, Louise Ng, Aylwin Elledge, Stephen J. Brass, Abraham L.
spellingShingle	Zhu, Jian Davoli, Teresa Perriera, Jill M. Chin, Christopher R. Gaiha, Gaurav D. John, Sinu P. Sigiollot, Frederic D. Gao, Geng Xu, Qikai Qu, Hongjing Pertel, Thomas Sims, Jennifer S. Smith, Jennifer A. Baker, Richard E. Maranda, Louise Ng, Aylwin Elledge, Stephen J. Brass, Abraham L. Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents
author_facet	Zhu, Jian Davoli, Teresa Perriera, Jill M. Chin, Christopher R. Gaiha, Gaurav D. John, Sinu P. Sigiollot, Frederic D. Gao, Geng Xu, Qikai Qu, Hongjing Pertel, Thomas Sims, Jennifer S. Smith, Jennifer A. Baker, Richard E. Maranda, Louise Ng, Aylwin Elledge, Stephen J. Brass, Abraham L.
author_sort	Zhu, Jian
title	Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents
title_short	Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents
title_full	Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents
title_fullStr	Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents
title_full_unstemmed	Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents
title_sort	comprehensive identification of host modulators of hiv-1 replication using multiple orthologous rnai reagents
description	RNAi screens have implicated hundreds of host proteins as HIV-1 dependency factors (HDFs). While informative, these early studies overlap poorly due to false positives and false negatives. To ameliorate these issues, we combined information from the existing HDF screens together with new screens performed with multiple orthologous RNAi reagents (MORR). In addition to being traditionally validated, the MORR screens and the historical HDF screens were quantitatively integrated by the adaptation of an established analysis program, RIGER, for the collective interpretation of each gene’s phenotypic significance. False positives were addressed by the removal of poorly expressed candidates through gene expression filtering, as well as with GESS, which identifies off-target effects. This workflow produced a quantitatively integrated network of genes that modulate HIV-1 replication. We further investigated the roles of GOLGI49, SEC13, and COG in HIV-1 replication. Collectively, the MORR-RIGER method minimized the caveats of RNAi screening and improved our understanding of HIV-1–host cell interactions.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926641/
_version_	1613601592708169728

Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents

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