Acyl-Coenzyme A Synthetase Long-Chain Family Member 4 Is Involved in Viral Replication Organelle Formation and Facilitates Virus Replication via Ferroptosis.
Acyl-Coenzyme A Synthetase Long-Chain Family Member 4 Is Involved in Viral Replication Organelle Formation and Facilitates Virus Replication via Ferroptosis.
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酰基辅酶A合成酶长链家族成员4参与病毒复制细胞器的形成并通过铁凋亡促进病毒复制。
DOI：
10.1128/mbio.02717-21
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发表时间：
2022-02-22
期刊：
影响因子：
6.4
通讯作者：
Shih SR
中科院分区：
文献类型：
--
作者：
Kung YA;Chiang HJ;Li ML;Gong YN;Chiu HP;Hung CT;Huang PN;Huang SY;Wang PY;Hsu TA;Brewer G;Shih SR
肠道病毒感染可引起严重的并发症，如脊髓灰质炎、脑炎、心肌炎、脑膜炎、神经性肺水肿，甚至死亡。在这里，我们使用全基因组CRISPR筛选来获得对肠道病毒利用宿主途径来增强复制和繁殖的机制的新见解。我们发现酰基辅酶A合成酶长链家族成员4（ACSL 4）参与病毒复制细胞器的形成。ACSL 4是铁凋亡（一种铁依赖性、非凋亡性程序性细胞死亡）的关键组分。我们的研究结果表明，肠道病毒和冠状病毒可以通过ACSL 4诱导铁凋亡。最重要的是，铁凋亡抑制剂，包括两种FDA批准的药物罗格列酮（ROSI; ACSL 4抑制剂）和吡格列酮（PIO; ACSL 4抑制剂），降低了人类肠道病毒和冠状病毒的病毒载量，表明ACSL 4是抵抗病毒感染的靶标。
Enterovirus infections can cause severe complications, such as poliomyelitis, encephalitis, myocarditis, meningitis, neurological pulmonary edema, and even death. Here, we used genome-wide CRISPR screens to gain new insight into the mechanism by which enteroviruses co-opt host pathways to potentiate replication and propagation. We found that acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) is involved in viral replication organelle formation. ACSL4 is a key component of ferroptosis, an iron-dependent, nonapoptotic programmed cell death. Our results indicated that enteroviruses and coronaviruses can induce ferroptosis via ACSL4. Most importantly, ferroptosis inhibitors, including two FDA-approved drugs, rosiglitazone (ROSI; ACSL4 inhibitor) and pioglitazone (PIO; ACSL4 inhibitor), decreased the viral load of human enteroviruses and coronaviruses, suggesting that ACSL4 is a target for counteracting viral infection.
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ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
影响因子：
14.8
作者：
Kagan VE;Mao G;Qu F;Angeli JP;Doll S;Croix CS;Dar HH;Liu B;Tyurin VA;Ritov VB;Kapralov AA;Amoscato AA;Jiang J;Anthonymuthu T;Mohammadyani D;Yang Q;Proneth B;Klein-Seetharaman J;Watkins S;Bahar I;Greenberger J;Mallampalli RK;Stockwell BR;Tyurina YY;Conrad M;Bayır H
通讯作者：
Bayır H
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
4
作者：
Dixon SJ;Winter GE;Musavi LS;Lee ED;Snijder B;Rebsamen M;Superti-Furga G;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
--
作者：
Corman VM;Muth D;Niemeyer D;Drosten C
通讯作者：
Drosten C