SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway

Sterile alpha motif (SAM) and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) inhibits HIV-1 replication in non-dividing cells by reducing the intracellular dNTP pool. SAMHD1 enhances spontaneous Apoptosis in cells, but its effects on HIV-1-induced Apoptosis and the underlying mechanisms remain unknown. Here we uncover a new mechanism by which SAMHD1 enhances HIV-1-induced Apoptosis in monocytic cells through the mitochondrial pathway. We found that endogenous SAMHD1 enhances Apoptosis levels induced by HIV-1 Infection in dividing THP-1 cells. Mechanistically, SAMHD1 expression decreases the mitochondrial membrane potential and promotes cytochrome c release induced by HIV-1 Infection in THP-1 cells, thereby enhancing mitochondrial apoptotic pathway. SAMHD1-enhanced Apoptosis is associated with increased expression of the pro-apoptotic protein BCL-2-interacting killer (BIK) in cells. We further demonstrated that BIK contributes to SAMHD1-enhanced Apoptosis during HIV-1 Infection. Overall, our results reveal an unappreciated regulatory mechanism of SAMHD1 in enhancing HIV-1-induced Apoptosis via the mitochondrial pathway in monocytic cells.

BCL-2-interacting killer; HIV-1 infection; SAMHD1; THP-1 cells; apoptosis; cytochrome c; mitochondrial membrane potential; mitochondrial pathway; monocytic cells.