A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors
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. He...
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/116682 https://orcid.org/0000-0002-4227-5163 https://orcid.org/0000-0002-1446-7256 |
| _version_ | 1826204992903577600 |
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| author | Park, Ryan J 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 Hacohen, Nir Walker, Bruce D Wang, Tim Sabatini, David Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Park, Ryan J 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 Hacohen, Nir Walker, Bruce D Wang, Tim Sabatini, David Lander, Eric Steven |
| author_sort | Park, Ryan J |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:05:22Z |
| format | Article |
| id | mit-1721.1/116682 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T13:05:22Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1166822022-09-28T11:56:24Z A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors Park, Ryan J 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 Hacohen, Nir Walker, Bruce D Wang, Tim Sabatini, David Lander, Eric Steven Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Wang, Tim Sabatini, David Lander, Eric Steven 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. 2018-06-28T18:42:57Z 2018-06-28T18:42:57Z 2016-12 2016-06 2018-06-28T16:16:23Z Article http://purl.org/eprint/type/JournalArticle 1061-4036 1546-1718 http://hdl.handle.net/1721.1/116682 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 https://orcid.org/0000-0002-4227-5163 https://orcid.org/0000-0002-1446-7256 http://dx.doi.org/10.1038/NG.3741 Nature Genetics Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Park, Ryan J 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 Hacohen, Nir Walker, Bruce D Wang, Tim Sabatini, David Lander, Eric Steven A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors |
| title | A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors |
| title_full | A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors |
| title_fullStr | A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors |
| title_full_unstemmed | A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors |
| title_short | A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors |
| title_sort | genome wide crispr screen identifies a restricted set of hiv host dependency factors |
| url | http://hdl.handle.net/1721.1/116682 https://orcid.org/0000-0002-4227-5163 https://orcid.org/0000-0002-1446-7256 |
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