CRISPRとHIV:ヒトの血液を使った新しい手法により、治療への道筋が明らかになる(CRISPR and HIV: New technique in human blood unveils potential paths toward cure)


HIV治療薬の鍵は、HIVが複製される仕組みにある可能性 Key to possible HIV cure may lie in mechanisms behind how it replicates

2022-04-01 ノースウェスタン大学



ヒト初代T細胞におけるHIV-宿主間相互作用の機能マップ A functional map of HIV-host interactions in primary human T cells

Joseph Hiatt,Judd F. Hultquist,Michael J. McGregor,Mehdi Bouhaddou,Ryan T. Leenay,Lacy M. Simons,Janet M. Young,Paige Haas,Theodore L. Roth,Victoria Tobin,Jason A. Wojcechowskyj,Jonathan M. Woo,Ujjwal Rathore,Devin A. Cavero,Eric Shifrut,Thong T. Nguyen,Kelsey M. Haas,Harmit S. Malik,Jennifer A. Doudna,Andrew P. May,Alexander Marson &Nevan J. Krogan
Nature Communications Published: 01 April 2022

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Human Immunodeficiency Virus (HIV) relies on host molecular machinery for replication. Systematic attempts to genetically or biochemically define these host factors have yielded hundreds of candidates, but few have been functionally validated in primary cells. Here, we target 426 genes previously implicated in the HIV lifecycle through protein interaction studies for CRISPR-Cas9-mediated knock-out in primary human CD4+ T cells in order to systematically assess their functional roles in HIV replication. We achieve efficient knockout (>50% of alleles) in 364 of the targeted genes and identify 86 candidate host factors that alter HIV infection. 47 of these factors validate by multiplex gene editing in independent donors, including 23 factors with restrictive activity. Both gene editing efficiencies and HIV-1 phenotypes are highly concordant among independent donors. Importantly, over half of these factors have not been previously described to play a functional role in HIV replication, providing numerous novel avenues for understanding HIV biology. These data further suggest that host-pathogen protein-protein interaction datasets offer an enriched source of candidates for functional host factor discovery and provide an improved understanding of the mechanics of HIV replication in primary T cells.