A virus-packageable CRISPR screen identifies host factors mediating interferon inhibition of HIV.

ABSTRACT: Interferon (IFN) inhibits HIV replication by inducing antiviral effectors. To comprehensively identify IFN-induced HIV restriction factors, we assembled a CRISPR sgRNA library of Interferon Stimulated Genes (ISGs) into a modified lentiviral vector that allows for packaging of sgRNA-encoding genomes in trans into budding HIV-1 particles. We observed that knockout of Zinc Antiviral Protein (ZAP) improved the performance of the screen due to ZAP-mediated inhibition of the vector. A small panel of IFN-induced HIV restriction factors, including MxB, IFITM1, Tetherin/BST2 and TRIM5alpha together explain the inhibitory effects of IFN on the CXCR4-tropic HIV-1 strain, HIV-1_LAI, in THP-1 cells. A second screen with a CCR5-tropic primary strain, HIV-1_Q23.BG505, described

SUBMITTER: OhAinle M 

PROVIDER: S-EPMC6286125 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature