Endothelial cells are not productively infected by SARS-CoV-2.
Endothelial cells are not productively infected by SARS-CoV-2.
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DOI：
10.1002/cti2.1350
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发表时间：
2021
影响因子：
5.8
通讯作者：
Gordon EJ
中科院分区：
文献类型：
--
作者：
Schimmel L;Chew KY;Stocks CJ;Yordanov TE;Essebier P;Kulasinghe A;Monkman J;Dos Santos Miggiolaro AFR;Cooper C;de Noronha L;Schroder K;Lagendijk AK;Labzin LI;Short KR;Gordon EJ
血栓形成和微血管并发症常见于已故的新冠肺炎患者。然而，这是由病毒直接感染内皮细胞还是由炎症诱导的内皮细胞激活引起的，仍然存在很大的争议。在这里，我们使用患者尸检样本、原代人内皮细胞和肺上皮-内皮细胞屏障的 体外模型。我们发现，原代人内皮细胞表达非常低水平的SARS-CoV-2受体ACE2和蛋白酶TMPRSS2，这会阻止它们产生病毒感染的能力，并限制它们产生传染性病毒的能力。因此，只有当内皮细胞过度表达ACE2或暴露在非常高浓度的SARS-CoV-2中时，内皮细胞才能被感染。我们还表明，在流动条件下，SARS-CoV-2不会感染3D血管中的内皮细胞。我们进一步证明，在共培养模型中，内皮细胞不会感染SARS-CoV-2。然而，内皮细胞确实感觉到并对邻近上皮细胞的感染做出反应，增加ICAM-1的表达并释放促炎细胞因子。综上所述，这些数据表明，在 体内，内皮细胞不太可能感染SARS-CoV-2，只有当邻近的肺上皮被剥离(基侧感染)或血液中存在高病毒载量(心尖感染)时，才可能发生感染。在这种情况下，虽然可能会发生SARS-CoV-2感染内皮细胞，但它不会促进病毒的放大。然而，内皮细胞仍可能通过感知邻近感染和启动对SARS-CoV-2的促炎反应而在SARS-CoV-2的发病过程中发挥关键作用。我们的研究表明，内皮细胞不会有效地感染SARS-CoV-2，但会对病毒产生促炎反应。
Thrombotic and microvascular complications are frequently seen in deceased COVID‐19 patients. However, whether this is caused by direct viral infection of the endothelium or inflammation‐induced endothelial activation remains highly contentious. Here, we use patient autopsy samples, primary human endothelial cells and an in vitro model of the pulmonary epithelial–endothelial cell barrier. We show that primary human endothelial cells express very low levels of the SARS‐CoV‐2 receptor ACE2 and the protease TMPRSS2, which blocks their capacity for productive viral infection, and limits their capacity to produce infectious virus. Accordingly, endothelial cells can only be infected when they overexpress ACE2, or are exposed to very high concentrations of SARS‐CoV‐2. We also show that SARS‐CoV‐2 does not infect endothelial cells in 3D vessels under flow conditions. We further demonstrate that in a co‐culture model endothelial cells are not infected with SARS‐CoV‐2. Endothelial cells do however sense and respond to infection in the adjacent epithelial cells, increasing ICAM‐1 expression and releasing pro‐inflammatory cytokines. Taken together, these data suggest that in vivo, endothelial cells are unlikely to be infected with SARS‐CoV‐2 and that infection may only occur if the adjacent pulmonary epithelium is denuded (basolateral infection) or a high viral load is present in the blood (apical infection). In such a scenario, whilst SARS‐CoV‐2 infection of the endothelium can occur, it does not contribute to viral amplification. However, endothelial cells may still play a key role in SARS‐CoV‐2 pathogenesis by sensing adjacent infection and mounting a pro‐inflammatory response to SARS‐CoV‐2. We show that endothelial cells are not productively infected with SARS‐CoV‐2 but mount a pro‐inflammatory response to the virus.
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DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
通讯作者：
Yamauchi Y
影响因子：
--
作者：
Andersson MI;Arancibia-Carcamo CV;Auckland K;Baillie JK;Barnes E;Beneke T;Bibi S;Brooks T;Carroll M;Crook D;Dingle K;Dold C;Downs LO;Dunn L;Eyre DW;Gilbert Jaramillo J;Harvala H;Hoosdally S;Ijaz S;James T;James W;Jeffery K;Justice A;Klenerman P;Knight JC;Knight M;Liu X;Lumley SF;Matthews PC;McNaughton AL;Mentzer AJ;Mongkolsapaya J;Oakley S;Oliveira MS;Peto T;Ploeg RJ;Ratcliff J;Robbins MJ;Roberts DJ;Rudkin J;Russell RA;Screaton G;Semple MG;Skelly D;Simmonds P;Stoesser N;Turtle L;Wareing S;Zambon M
通讯作者：
Zambon M
影响因子：
16.6
作者：
Aspalter IM;Gordon E;Dubrac A;Ragab A;Narloch J;Vizán P;Geudens I;Collins RT;Franco CA;Abrahams CL;Thurston G;Fruttiger M;Rosewell I;Eichmann A;Gerhardt H
通讯作者：
Gerhardt H
影响因子：
64.5
作者：
Aid M;Busman-Sahay K;Vidal SJ;Maliga Z;Bondoc S;Starke C;Terry M;Jacobson CA;Wrijil L;Ducat S;Brook OR;Miller AD;Porto M;Pellegrini KL;Pino M;Hoang TN;Chandrashekar A;Patel S;Stephenson K;Bosinger SE;Andersen H;Lewis MG;Hecht JL;Sorger PK;Martinot AJ;Estes JD;Barouch DH
通讯作者：
Barouch DH
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