A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors

Nat Genet. 2017 Feb;49(2):193-203. doi: 10.1038/ng.3741. Epub 2016 Dec 19.


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.

MeSH terms

  • Activated-Leukocyte Cell Adhesion Molecule / genetics
  • Cell Line
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Genome / genetics
  • HIV Infections / genetics*
  • HIV-1 / pathogenicity
  • Host-Pathogen Interactions / genetics*
  • Humans
  • Membrane Proteins / genetics
  • RNA Interference / physiology
  • Receptors, CCR5 / genetics
  • Sulfotransferases / genetics
  • Virus Replication / genetics


  • Activated-Leukocyte Cell Adhesion Molecule
  • CCR5 protein, human
  • Membrane Proteins
  • Receptors, CCR5
  • Sulfotransferases
  • TPST2 protein, human