dc.contributor.author | Park, Ryan J | |
dc.contributor.author | Koundakjian, Dylan | |
dc.contributor.author | Hultquist, Judd F | |
dc.contributor.author | Lamothe-Molina, Pedro | |
dc.contributor.author | Monel, Blandine | |
dc.contributor.author | Schumann, Kathrin | |
dc.contributor.author | Yu, Haiyan | |
dc.contributor.author | Krupzcak, Kevin M | |
dc.contributor.author | Garcia-Beltran, Wilfredo | |
dc.contributor.author | Piechocka-Trocha, Alicja | |
dc.contributor.author | Krogan, Nevan J | |
dc.contributor.author | Marson, Alexander | |
dc.contributor.author | Hacohen, Nir | |
dc.contributor.author | Walker, Bruce D | |
dc.contributor.author | Wang, Tim | |
dc.contributor.author | Sabatini, David | |
dc.contributor.author | Lander, Eric Steven | |
dc.date.accessioned | 2018-06-28T18:42:57Z | |
dc.date.available | 2018-06-28T18:42:57Z | |
dc.date.issued | 2016-12 | |
dc.date.submitted | 2016-06 | |
dc.identifier.issn | 1061-4036 | |
dc.identifier.issn | 1546-1718 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/116682 | |
dc.description.abstract | Host proteins are essential for HIV entry and replication and can be important nonviral therapeutic targets. Large-scale RNA interference (RNAi)-based screens have identified nearly a thousand candidate host factors, but there is little agreement among studies and few factors have been validated. Here we demonstrate that a genome-wide CRISPR-based screen identifies host factors in a physiologically relevant cell system. We identify five factors, including the HIV co-receptors CD4 and CCR5, that are required for HIV infection yet are dispensable for cellular proliferation and viability. Tyrosylprotein sulfotransferase 2 (TPST2) and solute carrier family 35 member B2 (SLC35B2) function in a common pathway to sulfate CCR5 on extracellular tyrosine residues, facilitating CCR5 recognition by the HIV envelope. Activated leukocyte cell adhesion molecule (ALCAM) mediates cell aggregation, which is required for cell-to-cell HIV transmission. We validated these pathways in primary human CD4 + T cells through Cas9-mediated knockout and antibody blockade. Our findings indicate that HIV infection and replication rely on a limited set of host-dispensable genes and suggest that these pathways can be studied for therapeutic intervention. | en_US |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1038/NG.3741 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Park, Ryan J et al. “A Genome-Wide CRISPR Screen Identifies a Restricted Set of HIV Host Dependency Factors.” Nature Genetics 49, 2 (December 2016): 193–203 © 2017 Nature America, Inc., part of Springer Nature | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Institute for Medical Engineering & Science | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Wang, Tim | |
dc.contributor.mitauthor | Sabatini, David | |
dc.contributor.mitauthor | Lander, Eric Steven | |
dc.relation.journal | Nature Genetics | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2018-06-28T16:16:23Z | |
dspace.orderedauthors | Park, Ryan J; Wang, Tim; Koundakjian, Dylan; Hultquist, Judd F; Lamothe-Molina, Pedro; Monel, Blandine; Schumann, Kathrin; Yu, Haiyan; Krupzcak, Kevin M; Garcia-Beltran, Wilfredo; Piechocka-Trocha, Alicja; Krogan, Nevan J; Marson, Alexander; Sabatini, David M; Lander, Eric S; Hacohen, Nir; Walker, Bruce D | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-4227-5163 | |
dc.identifier.orcid | https://orcid.org/0000-0002-1446-7256 | |
mit.license | OPEN_ACCESS_POLICY | en_US |