A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors
Name
nihms875593.pdf
Size
1.83 MB
Format
Adobe PDF
Checksum (MD5)
35835ea14f434b1314c04a956429bcbb
Author(s)
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
Date Issued
December 2016
Journal
Nature Genetics
Publisher
Nature Publishing Group
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
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/NG.3741
