By inactivating any one of five human genes, scientists can prevent HIV from entering and growing in immune cells. 

Antiviral therapies targeting host genes that the virus depends on, rather than targeting the virus itself, are promising because these genes do not mutate as frequently as viruses do. This could avoid the development of drug resistance.

Researchers screened the genome of human T cells and identified five genes not essential to cell survival whose inactivation protected cells from HIV infection. Cultured cells lacking these genes resisted HIV infection.

The genes encode proteins that facilitate virus entry into human cells, and one that mediates cell aggregation, which allows the virus to spread between cells. These genes include 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.

Authors validated these pathways in primary human CD4⁺ T cells through Cas9-mediated knockout and antibody blockade. The authors say their approach could also be used to find drug targets for other pandemic viruses.

http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3741.html