연사 : 안광석교수 (서울대학교 생명과학부)
연제 : Cell intrinsic immunity to retroviruses
일시 : 2015년 5월 8일 (금) 오후 4시
장소 : 하나과학관 A동 101호
초청교수 : 안병윤교수
Abstract
SAMHD1 is an HIV-1 restriction factor that blocks virus replication in dendritic and other myeloid cells. SAMHD1 has recently identified as a deoxynucleoside triphosphate triphosphohydrolase (dNTPase) and most likely inhibits HIV-1 infection by depleting the intracellular dNTP pool. Mutations in SAMHD1 result in Aicardi-Gouti？res syndrome (AGS), a genetic autoimmune disease characterized by elevated type I interferon production and clinical symptoms mimicking a congenital viral infection. Given the known ribonuclease activities of the AGS-associated proteins TREX1 and RNASEH2, it is possible that the potential ribonuclease activity of SAMHD1 plays an important role in HIV-1 restriction. Here, we show that SAMHD1 is a 3′to 5′ single-stranded RNA-specific exoribonuclease and that this ribonuclease activity is required for the inhibition of HIV-1 replication. Independent of its known dNTPase activity, SAMHD1 directly degrades the genomic HIV-1 RNA during the early phases of infection, leading to the inhibition of reverse transcription. In addition, SAMHD1 selectively restricted retroviral replication, but did not affect the replication of other common non-retro RNA genome viruses, suggesting that the RNase-mediated antiviral function of SAMHD1 is limited to retroviruses. The presence of dual catalytic functions that antagonize HIV-1 in a single enzyme strengthens the rationale for targeting SAMHD1 in anti-HIV therapies. Given our findings and the fact that the AGS phenotype is thought to be induced by the accumulation of nucleic acids, the intrinsic cellular function of SAMHD1 is likely to recognize and dispose of the endogenous RNA byproducts, thereby preventing the otherwise detrimental activation of innate immune responses.