Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion.
Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion.
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DOI：
10.1002/jmv.28478
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发表时间：
2023-02
影响因子：
12.7
通讯作者：
Li, Chia-Wei
中科院分区：
文献类型：
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作者：
Huang, Hsiang-Chi;Wang, Shih-Han;Fang, Guo-Chen;Chou, Wen-Cheng;Liao, Chun-Che;Sun, Cheng-Pu;Jan, Jia-Tsrong;Ma, Hsiu-Hua;Ko, Hui-Ying;Ko, Yi-An;Chiang, Ming-Tsai;Liang, Jian-Jong;Kuo, Chun-Tse;Lee, Te-An;Morales-Scheihing, Diego;Shen, Chen-Yang;Chen, Shih-Yu;McCullough, Louise D.;Cui, Lu;Wernig, Gerlinde;Tao, Mi-Hua;Lin, Yi-Ling;Chang, Yao-Ming;Wang, Shu-Ping;Lai, Yun-Ju;Li, Chia-Wei
患有严重COVID-19的患者通常患有淋巴细胞减少症，这与T细胞隔离、细胞因子风暴和死亡率有关。然而，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）如何诱导淋巴细胞减少症在很大程度上仍然未知。在这里，我们研究了SARS-CoV-2感染细胞产生细胞因子的转录组学特征和表观基因组学改变。我们采用反向时间顺序基因共表达网络方法来分析时间序列RNA测序数据，揭示病毒逃逸后期的表观遗传修饰。此外，我们通过H3 K4 me 3染色质免疫沉淀测序的表观遗传学分析，确定了SARS-CoV-2激活的核因子-κB（NF-κB）和干扰素调节因子1（IRF 1）通路对病毒感染和COVID-19严重程度的贡献。交叉引用我们的转录组学和表观基因组学数据集显示，NF-κB和IRF 1途径的偶联介导了程序性死亡配体1（PD-L1）免疫抑制程序。有趣的是，我们观察到Omicron感染细胞中的PD-L1表达高于SARS-CoV-2感染细胞。在病毒感染的AAV-hACE 2小鼠的早期阶段阻断PD-L1可显著恢复淋巴细胞计数并降低炎性细胞因子水平。我们的研究结果表明，靶向SARS-CoV-2-介导的NF-κB和IRF 1-PD-L1轴可能是降低COVID-19严重程度的替代策略。
Patients with severe COVID‐19 often suffer from lymphopenia, which is linked to T‐cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS‐CoV‐2‐infected cells. We adopted a reverse time‐order gene coexpression network approach to analyze time‐series RNA‐sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS‐CoV‐2‐activated nuclear factor‐κB (NF‐κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID‐19 severity through epigenetic analysis of H3K4me3 chromatin immunoprecipitation sequencing. Cross‐referencing our transcriptomic and epigenomic data sets revealed that coupling NF‐κB and IRF1 pathways mediate programmed death ligand‐1 (PD‐L1) immunosuppressive programs. Interestingly, we observed higher PD‐L1 expression in Omicron‐infected cells than SARS‐CoV‐2 infected cells. Blocking PD‐L1 at an early stage of virally‐infected AAV‐hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS‐CoV‐2‐mediated NF‐κB and IRF1‐PD‐L1 axis may represent an alternative strategy to reduce COVID‐19 severity.
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影响因子：
16.6
作者：
Ferreira-Gomes M;Kruglov A;Durek P;Heinrich F;Tizian C;Heinz GA;Pascual-Reguant A;Du W;Mothes R;Fan C;Frischbutter S;Habenicht K;Budzinski L;Ninnemann J;Jani PK;Guerra GM;Lehmann K;Matz M;Ostendorf L;Heiberger L;Chang HD;Bauherr S;Maurer M;Schönrich G;Raftery M;Kallinich T;Mall MA;Angermair S;Treskatsch S;Dörner T;Corman VM;Diefenbach A;Volk HD;Elezkurtaj S;Winkler TH;Dong J;Hauser AE;Radbruch H;Witkowski M;Melchers F;Radbruch A;Mashreghi MF
通讯作者：
Mashreghi MF
DOI：
10.1016/j.biopha.2021.112420
发表时间：
2022-01
期刊：
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
影响因子：
--
作者：
Farahani M;Niknam Z;Mohammadi Amirabad L;Amiri-Dashatan N;Koushki M;Nemati M;Danesh Pouya F;Rezaei-Tavirani M;Rasmi Y;Tayebi L
通讯作者：
Tayebi L
影响因子：
7.3
作者：
Bhaskar, Sonu;Sinha, Akansha;Kutty, Shelby
通讯作者：
Kutty, Shelby
影响因子：
7.3
作者：
Diao, Bo;Wang, Chenhui;Chen, Yongwen
通讯作者：
Chen, Yongwen
影响因子：
5.7
作者：
Atlante S;Mongelli A;Barbi V;Martelli F;Farsetti A;Gaetano C
通讯作者：
Gaetano C