Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis.
Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis.
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人体免疫细胞的 SARS-CoV-2 感染的抗体依赖性增强：体外评估提供了对 COVID-19 发病机制的见解
DOI：
10.3390/v13122483
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发表时间：
2021-12-11
期刊：
影响因子：
--
通讯作者：
Zhou P
中科院分区：
文献类型：
--
作者：
Shen XR;Li Q;Li HL;Wang X;Wang Q;Zheng XS;Geng R;Zhang YL;Li B;Jiang RD;Liu MQ;Zhu Y;Zhang W;Yang XL;Peng K;Zhou P
COVID-19患者感染后一般会产生SARS-CoV-2抗体，抗体水平与疾病严重程度呈正相关。病毒抗体是否通过抗体依赖性增强（ADE）加剧COVID-19仍不完全清楚。在这里，我们进行了体外评估是否恢复期血清增强SARS-CoV-2感染或诱导免疫细胞过度免疫反应。我们的数据显示，来自COVID-19患者的恢复期血清可以增强SARS-CoV-2对表达不同水平FcγR的原代B细胞、巨噬细胞和单核细胞的感染。我们还确定了与ADE相关的因素，并发现这些因素具有时间依赖性，而不是病毒剂量依赖性。此外，当检测从不同患者采集的血清样本时，ADE效应与中和滴度或RBD抗体水平无关。然而，在显示ADE效应的给定样品中，中等水平的它高于低或高稀释度，这与登革热相似。最后，我们证明了更多的病毒基因或失调的宿主免疫基因表达ADE条件下相比，无血清感染组。总的来说，我们的研究提供了对高病毒抗体滴度与COVID-19重症患者严重肺部病理学相关性的理解。
Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.
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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
影响因子：
5.4
作者：
Jaume, Martial;Yip, Ming S.;Peiris, J. S. Malik
通讯作者：
Peiris, J. S. Malik
影响因子：
1.2
作者：
Takano, Tomomi;Kawakami, Chisako;Hohdatsu, Tsutomu
通讯作者：
Hohdatsu, Tsutomu
影响因子：
5.4
作者：
Wan, Yushun;Shang, Jian;Li, Fang
通讯作者：
Li, Fang
影响因子：
64.8
作者：
Arvin, Ann M.;Fink, Katja;Virgin, Herbert W.
通讯作者：
Virgin, Herbert W.