The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors
Open accessAbstract
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.
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Cites
Genome-scale CRISPR-Cas9 knockout screening in human cells
Shalem, O., Sanjana, N. E., Hartenian, E., Shi, X., Scott, D. A., Mikkelsen, T. S., Heckl, D., Ebert, B. L., Root, D. E., Doench, J. G., et al. (2014) · Science · doi:10.1126/science.1247005 · Cited by 5,234
Identification and characterization of essential genes in the human genome
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Self-citationIdentification of host proteins required for HIV infection through a functional genomic screen
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Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV
Tebas, P., Stein, D., Tang, W. W., Frank, I., Wang, S. Q., Lee, G., Spratt, S. K., Surosky, R. T., Giedlin, M. A., Nichol, G., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1300662 · Cited by 1,357
Global landscape of HIV–human protein complexes
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Self-citationA sensitive and specific enzyme-based assay detecting HIV-1 virion fusion in primary T lymphocytes
Cavrois, M., de Noronha, C., & Greene, W. C. (2002) · Nature Biotechnology · doi:10.1038/nbt745 · Cited by 475
Inefficient human immunodeficiency virus replication in mobile lymphocytes
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Sowd, G. A., Serrao, E., Wang, H., Wang, W., Fadel, H. J., Poeschla, E. M., & Engelman, A. N. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1524213113 · Cited by 249
LEDGF/p75 interacts with mRNA splicing factors and targets HIV-1 integration to highly spliced genes
Singh, P. K., Plumb, M. R., Ferris, A. L., Iben, J. R., Wu, X., Fadel, H. J., Luke, B. T., Esnault, C., Poeschla, E. M., Hughes, S. H., et al. (2015) · Genes & Development · doi:10.1101/gad.267609.115 · Cited by 109
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Am I ready for CRISPR? A user's guide to genetic screens
Doench, J. G. (2018) · Nature Reviews Genetics · doi:10.1038/nrg.2017.97 · Cited by 452
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Li, Y., Ran, Q., Duan, Q., Jin, J., Wang, Y., Yu, L., Wang, C., Zhu, Z., Chen, X., Weng, L., et al. (2024) · Nature · doi:10.1038/s41586-023-06983-9 · Cited by 367
A new era in functional genomics screens
Przybyla, L., & Gilbert, L. A. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00409-w · Cited by 281
Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication
Han, J., Perez, J. T., Chen, C., Li, Y., Benitez, A., Kandasamy, M., Lee, Y., Andrade, J., tenOever, B., & Manicassamy, B. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.045 · Cited by 266
Metadata
- Authors
- Park, R. J., Wang, T., Koundakjian, D., Hultquist, J. F., Lamothe-Molina, P., Monel, B., Schumann, K., Yu, H., Krupzcak, K. M., Garcia-Beltran, W., Piechocka-Trocha, A., Krogan, N. J., Marson, A., Sabatini, D. M., Lander, E. S., Hacohen, N., & Walker, B. D.
- Venue
- Nature Genetics
- Published
- 2016-12-19
- Volume
- 49
- Issue
- 2
- Pages
- 193-203
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2565680402
- Cited by
- 333
- References
- 9
- FWCI
- 23.99
- Type
- journal article
- Language
- en
- Open access
- green
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