Restriction factors are anti-viral proteins that host cells produce to restrict the multiplication of viruses. The human restriction factor SAMHD1 has long been known to prevent HIV-1 from infecting resting T cells, macrophages and dendritic cells. Precisely how SAMHD1 blocks HIV-1 in humans has not been clear, with some evidence pointing to SAMHD1’s enzymatic activity as playing a role.

In research published online on February 2 in Nature Communications, Felipe Diaz-Griffero, Ph.D., and colleagues show, for the first time, that SAMHD1’s direct interaction with nucleic acids in the HIV-1 genome—and not its enzymatic activity—inhibits infection. The findings suggest that HIV and other viral pathogens can be attacked using therapies that directly target their genomes.

Dr. Diaz-Griffero is professor of microbiology & immunology and Elsie Wachtel Faculty Scholar at Einstein.