ACE2-independent infection of T lymphocytes by SARS-CoV-2.
ACE2-independent infection of T lymphocytes by SARS-CoV-2.
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SARS-CoV-2 不依赖 ACE2 的 T 淋巴细胞感染
DOI：
10.1038/s41392-022-00919-x
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发表时间：
2022-03-11
影响因子：
39.3
通讯作者：
Zhou P
中科院分区：
文献类型：
--
作者：
Shen XR;Geng R;Li Q;Chen Y;Li SF;Wang Q;Min J;Yang Y;Li B;Jiang RD;Wang X;Zheng XS;Zhu Y;Jia JK;Yang XL;Liu MQ;Gong QC;Zhang YL;Guan ZQ;Li HL;Zheng ZH;Shi ZL;Zhang HL;Peng K;Zhou P
SARS-CoV-2诱导重症COVID-19患者显著淋巴细胞减少。然而，淋巴细胞是否是病毒感染的靶点尚未确定，尽管已在患者的T细胞中鉴定出SARS-CoV-2 RNA或抗原。在这里，我们证实了SARS-CoV-2病毒抗原可以在患者外周血（pbc）或死后肺T细胞中检测到，并且感染性病毒也可以从病毒抗原阳性的pbc中检测到。接下来，我们在体外证明了SARS-CoV-2感染T淋巴细胞，最好是激活CD4 + T细胞。感染后，在T细胞中可检测到病毒RNA、亚基因组RNA、病毒蛋白或病毒颗粒。此外，我们通过ACE2敲除或受体阻断实验表明，感染是spike-ACE2/ tmprss2独立的。接下来，我们证明了患者的病毒抗原阳性T细胞发生了明显的凋亡。体外感染T细胞诱导细胞死亡，这可能在线粒体ros - hif -1a依赖途径中发生。最后，我们证明，与其他已知受体列表相比，LFA-1蛋白更有可能是介导T细胞中SARS-CoV-2感染的进入分子。LFA-1蛋白只在多个白细胞中表达。总的来说，这项工作证实了SARS-CoV-2以刺突- ace2独立的方式感染T细胞，这为SARS-CoV-2诱导的COVID-19患者淋巴细胞减少的潜在机制提供了新的见解。
SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.
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DOI：
10.1186/cc14003
发表时间：
2014-08-01
期刊：
Critical care (London, England)
影响因子：
--
作者：
Darcy CJ;Minigo G;Piera KA;Davis JS;McNeil YR;Chen Y;Volkheimer AD;Weinberg JB;Anstey NM;Woodberry T
通讯作者：
Woodberry T
影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
64.8
作者：
Delorey TM;Ziegler CGK;Heimberg G;Normand R;Yang Y;Segerstolpe Å;Abbondanza D;Fleming SJ;Subramanian A;Montoro DT;Jagadeesh KA;Dey KK;Sen P;Slyper M;Pita-Juárez YH;Phillips D;Biermann J;Bloom-Ackermann Z;Barkas N;Ganna A;Gomez J;Melms JC;Katsyv I;Normandin E;Naderi P;Popov YV;Raju SS;Niezen S;Tsai LT;Siddle KJ;Sud M;Tran VM;Vellarikkal SK;Wang Y;Amir-Zilberstein L;Atri DS;Beechem J;Brook OR;Chen J;Divakar P;Dorceus P;Engreitz JM;Essene A;Fitzgerald DM;Fropf R;Gazal S;Gould J;Grzyb J;Harvey T;Hecht J;Hether T;Jané-Valbuena J;Leney-Greene M;Ma H;McCabe C;McLoughlin DE;Miller EM;Muus C;Niemi M;Padera R;Pan L;Pant D;Pe'er C;Pfiffner-Borges J;Pinto CJ;Plaisted J;Reeves J;Ross M;Rudy M;Rueckert EH;Siciliano M;Sturm A;Todres E;Waghray A;Warren S;Zhang S;Zollinger DR;Cosimi L;Gupta RM;Hacohen N;Hibshoosh H;Hide W;Price AL;Rajagopal J;Tata PR;Riedel S;Szabo G;Tickle TL;Ellinor PT;Hung D;Sabeti PC;Novak R;Rogers R;Ingber DE;Jiang ZG;Juric D;Babadi M;Farhi SL;Izar B;Stone JR;Vlachos IS;Solomon IH;Ashenberg O;Porter CBM;Li B;Shalek AK;Villani AC;Rozenblatt-Rosen O;Regev A
通讯作者：
Regev A
多器官感染和SAR的发病机理。
影响因子：
15.3
作者：
Gu, Jiang;Gong, Encong;Zhang, Bo;Zheng, Jie;Gao, Zifen;Zhong, Yanfeng;Zou, Wanzhong;Zhan, Jun;Wang, Shenglan;Xie, Zhigang;Zhuang, Hui;Wu, Bingquan;Zhong, Haohao;Shao, Hongquan;Fang, Weigang;Gao, Dongshia;Pei, Fei;Li, Xingwang;He, Zhongpin;Xu, Danzhen;Shi, Xeying;Anderson, Virginia M;Leong, Anthony S-Y
通讯作者：
Leong, Anthony S-Y
影响因子：
3.7
作者：
Haenel, Karen;Willbold, Dieter
通讯作者：
Willbold, Dieter