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Comprehensive identification of host modulators of HIV-1 replication using multiple orthologous RNAi reagents.

Abstract：

: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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Zhu J,Davoli T,Perriera JM,Chin CR,Gaiha GD,John SP,Sigiollot FD,Gao G,Xu Q,Qu H,Pertel T,Sims JS,Smith JA,Baker RE,Maranda L,Ng A,Elledge SJ,Brass AL

doi

10.1016/j.celrep.2014.09.031

subject

Has Abstract

pub_date

2014-10-23 00:00:00

pages

752-66

issue

2

issn

2211-1247

pii

S2211-1247(14)00814-6

journal_volume

9

pub_type

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