Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein

摘要: Macrophages and dendritic cells have key roles in viral infections, providing virus reservoirs that frequently resist antiviral therapies linking innate detection to adaptive immune responses. Human immunodeficiency 1 (HIV-1) fails transduce has a reduced ability macrophages, due an as yet uncharacterized mechanism inhibits infection by interfering with efficient synthesis of complementary DNA. In contrast, HIV-2 related simian viruses (SIVsm/mac) myeloid efficiently owing their virion-associated Vpx accessory proteins, which counteract the restrictive mechanism. Here we show inhibition HIV-1 macrophages involves cellular SAM domain HD domain-containing protein (SAMHD1). relieves lentivirus loading SAMHD1 onto CRL4(DCAF1) E3 ubiquitin ligase, leading highly proteasome-dependent degradation protein. Mutations cause Aicardi-Goutieres syndrome, disease produces phenotype mimics effects congenital infection. Failure dispose endogenous nucleic acid debris syndrome results inappropriate triggering responses via cytosolic acids sensors. Thus, our findings are defended from prevents unwanted interferon response triggered self acids, uncover intricate relationship between mechanisms control retroviral pathogens.