A virus-packageable CRISPR screen identifies host factors mediating interferon inhibition of HIV
| Title: | A virus-packageable CRISPR screen identifies host factors mediating interferon inhibition of HIV |
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| Authors: | Molly OhAinle, Louisa Helms, Jolien Vermeire, Ferdinand Roesch, Daryl Humes, Ryan Basom, Jeffrey J Delrow, Julie Overbaugh, Michael Emerman |
| Source: | eLife, Vol 7 (2018) |
| Publisher Information: | eLife Sciences Publications Ltd, 2018. |
| Publication Year: | 2018 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | CRISPR, HIV, interferon-stimulated genes, restriction factor, screen, virus replication, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | 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-1LAI, in THP-1 cells. A second screen with a CCR5-tropic primary strain, HIV-1Q23.BG505, described an overlapping, but non-identical, panel of restriction factors. Further, this screen also identifies HIV dependency factors. The ability of IFN-induced restriction factors to inhibit HIV strains to replicate in human cells suggests that these human restriction factors are incompletely antagonized.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter). |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/39823; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.39823 |
| Access URL: | https://doaj.org/article/d00363c9c13a413a99b3da1064c12277 |
| Accession Number: | edsdoj.00363c9c13a413a99b3da1064c12277 |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.39823 |
| Published in: | eLife |
| Language: | English |