Role of Intracellular Distribution of Feline and Bovine SAMHD1 Proteins in Lentiviral Restriction  

作　　者：Chu Wang Lina Meng Jialin Wang Kaikai Zhang Sizhu Duan Pengyu Ren Yingzhe Wei Xinyu Fu Bin Yu Jiaxin Wu Xianghui Yu 

机构地区：[1]National Engineering Laboratory for AIDS Vaccine,School of Life Sciences,Jilin University,Changchun 130012,China [2]The First Hospital and Institute of Immunology,Jilin University,Changchun 130012,China [3]Key Laboratory for Molecular Enzymology and Engineering,the Ministry of Education,School of Life Sciences,Jilin University,Changchun 130012,China

出　　处：《Virologica Sinica》2021年第5期981-996,共16页中国病毒学（英文版）

基　　金：funded by the National Natural Science Foundation of China(31270807);the Key Projects in the National Science&Technology Pillar Program in the Thirteenth Five-year Plan Period(2018ZX10731101-002-003 and 2018ZX10731101-001-020);Program for Jilin University Science and Technology Innovative Research Team(JLUSTIRT)(2017TD05);National Postdoctoral Program for Innovative Talents(BX20180124);China Postdoctoral Science Foundation(2018M641786);Science and Technology Development Project of Jilin Province(20200901030SF)。

摘　　要：Human SAMHD1(h SAM)restricts lentiviruses at the reverse transcription step through its d NTP triphosphohydrolase(d NTPase)activity.Besides humans,several mammalian species such as cats and cows that carry their own lentiviruses also express SAMHD1.However,the intracellular distribution of feline and bovine SAMHD1(f SAM and b SAM)and its significance in their lentiviral restriction function is not known.Here,we demonstrated that f SAM and b SAM were both predominantly localized to the nucleus and nuclear localization signal(11KRPR14)-deleted f SAM and b SAM relocalized to the cytoplasm.Both cytoplasmic f SAM and b SAM retained the antiviral function against different lentiviruses and cytoplasmic f SAM could restrict Vpx-encoding SIV and HIV-2 more efficiently than its wild-type(WT)protein as cytoplasmic h SAM.Further investigation revealed that cytoplasmic f SAM was resistant to Vpx-induced degradation like cytoplasmic h SAM,while cytoplasmic b SAM was not,but they all demonstrated the same in vitro d NTPase activity and all could interact with Vpx as their WT proteins,indicating that cytoplasmic h SAM and f SAM can suppress more SIV and HIV-2 by being less sensitive to Vpx-mediated degradation.Our results suggested that f SAM-and b SAM-mediated lentiviral restriction does not require their nuclear localization and that f SAM shares more common features with h SAM.These findings may provide insights for the establishment of alternative animal models to study SAMHD1 in vivo.

关 键 词：SAMHD1 Feline SAMHD1(fSAM) Bovine SAMHD1(bSAM) Nuclear localization signal(NLS) VPX Degradation Viral restriction 

分 类 号：R392-33[医药卫生—免疫学]