Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants.
Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants.
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DOI：
10.1073/pnas.2221652120
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发表时间：
2023-04-18
影响因子：
11.1
通讯作者：
Iwasaki, Akiko
中科院分区：
文献类型：
--
作者：
Moriyama, Miyu;Lucas, Carolina;Monteiro, Valter Silva;Iwasaki, Akiko
许多病原病毒已经开发出逃避宿主 CD8+ T 细胞介导的清除的策略。在这里，我们证明了 SARS-CoV-2 编码多种病毒因子，可以调节宿主细胞中主要组织相容性复合物 I 类 (MHC-I) 的表达。我们发现，在体内 SARS-CoV-2 期间，MHC-I 上调受到强烈抑制，但流感病毒感染期间则没有。值得注意的是，与原始菌株和早期关注的 SARS-CoV-2 变体 (VOC) 相比，Omicron 亚变体表现出增强的抑制 MHC-I 的能力。我们在 Omicron 亚变体共有的 E 蛋白中发现了一个突变，该突变进一步抑制了 MHC-I 的表达。我们的结果表明 SARS-CoV-2 具有固有的强大阻碍 MHC-I 表达的能力，并证明 Omicron 亚变体已经进化出了更优化的逃避 CD8 T 细胞识别的能力。严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 相关变体 (VOC) 具有突变，这些突变会赋予 Spike 蛋白内的中和抗体抗性，并与突破性感染和再感染相关。相比之下，人们对 VOC 逃避 CD8+ T 细胞介导的免疫力知之甚少。在这里，我们证明所有 SARS-CoV-2 VOC 都具有抑制主要组织相容性复合物 I 类 (MHC-I) 表达的能力。我们鉴定了一些有助于抑制 MHC I 表达的病毒基因。值得注意的是，MHC-I 的上调在 SARS-CoV-2 后受到强烈抑制，但在体内感染流感病毒后却没有受到抑制。虽然早期的 VOC 具有与祖先菌株相似的抑制 MHC-I 的能力，但 Omicron 亚变体表现出更强的抑制表面 MHC-I 表达的能力。我们发现了 Omicron E 蛋白中的一个常见突变，该突变进一步抑制了 MHC-I 的表达。总的来说，我们的数据表明，除了逃避中和抗体之外，Omicron 亚变体成功引起突破性感染和再感染可能部分归因于其对 T 细胞识别的优化逃避。
Numerous pathogenic viruses have developed strategies to evade host CD8+ T cell-mediated clearance. Here, we demonstrated that SARS-CoV-2 encodes multiple viral factors that can modulate major histocompatibility complex class I (MHC-I) expression in the host cells. We found that MHC-I upregulation was strongly suppressed during SARS-CoV-2, but not influenza virus infection, in vivo. Notably, the Omicron subvariants showed an enhanced ability to suppress MHC-I compared to the original strain and the earlier SARS-CoV-2 variants of concern (VOCs). We identified a mutation in the E protein shared by the Omicron subvariants that further suppressed MHC-I expression. Our results point to the inherently strong ability of SARS-CoV-2 to hinder MHC-I expression and demonstrated that Omicron subvariants have evolved an even more optimized capacity to evade CD8 T cell recognition. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that all SARS-CoV-2 VOCs possess the ability to suppress major histocompatibility complex class I (MHC-I) expression. We identified several viral genes that contribute to the suppression of MHC I expression. Notably, MHC-I upregulation was strongly inhibited after SARS-CoV-2 but not influenza virus infection in vivo. While earlier VOCs possess similar capacity as the ancestral strain to suppress MHC-I, the Omicron subvariants exhibited a greater ability to suppress surface MHC-I expression. We identified a common mutation in the E protein of Omicron that further suppressed MHC-I expression. Collectively, our data suggest that in addition to escaping from neutralizing antibodies, the success of Omicron subvariants to cause breakthrough infection and reinfection may in part be due to its optimized evasion from T cell recognition.
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影响因子：
32.4
作者：
Ferretti AP;Kula T;Wang Y;Nguyen DMV;Weinheimer A;Dunlap GS;Xu Q;Nabilsi N;Perullo CR;Cristofaro AW;Whitton HJ;Virbasius A;Olivier KJ Jr;Buckner LR;Alistar AT;Whitman ED;Bertino SA;Chattopadhyay S;MacBeath G
通讯作者：
MacBeath G
影响因子：
64.8
作者：
COVID-19 Host Genetics Initiative
通讯作者：
COVID-19 Host Genetics Initiative
影响因子：
3.6
作者：
Jongsma, Marlieke L. M.;Guarda, Greta;Spaapen, Robbert M.
通讯作者：
Spaapen, Robbert M.
DOI：
10.1073/pnas.2203760119
发表时间：
2022-08-09
影响因子：
11.1
作者：
通讯作者：
--
影响因子：
24.8
作者：
GeurtsvanKessel CH;Geers D;Schmitz KS;Mykytyn AZ;Lamers MM;Bogers S;Scherbeijn S;Gommers L;Sablerolles RSG;Nieuwkoop NN;Rijsbergen LC;van Dijk LLA;de Wilde J;Alblas K;Breugem TI;Rijnders BJA;de Jager H;Weiskopf D;van der Kuy PHM;Sette A;Koopmans MPG;Grifoni A;Haagmans BL;de Vries RD
通讯作者：
de Vries RD