Novel cellular factors essential for HIV infection are identified using CRISPR/Cas9 genome editing technology in a paper published online this week in Nature Genetics. Importantly, inactivation of these factors prevents HIV infection but does not affect cell viability, making them promising candidate targets of novel drugs or gene therapy.
David Sabatini, Eric Lander, Nir Hacohen, Bruce Walker and colleagues used CRISPR/Cas9 to create a library of T cells, the natural host for HIV, in which the vast majority of genes in the human genome were inactivated individually. They then infected these cells with HIV and screened for genes that, when mutated, rendered the cells resistant to HIV infection without affecting normal cell functions. They identified five such genes in total-two of which were already known to be important for HIV infection, along with three novel factors-and validated their findings with follow-up functional experiments and in T cells isolated from healthy human donors.
Previous screens for host factors important for HIV infection that used older technology were able to identify many candidate targets, but there was little overlap between screens, suggesting high rates of false positive results. The results from the current screen could represent strong candidates for targets of new anti-HIV therapies.