Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection.
Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection.
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抑制 ACSL1 相关铁死亡可抑制小鼠冠状病毒感染
DOI：
10.3390/v13122383
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发表时间：
2021-11-28
期刊：
影响因子：
--
通讯作者：
You F
中科院分区：
文献类型：
--
作者：
Xia H;Zhang Z;You F
小鼠肝炎病毒A59株（MHV-A59）可引起感染细胞的凋亡、坏死和凋亡，尤其是小鼠巨噬细胞。然而，是否ferroptosis，最近确定的溶解性细胞死亡的形式，参与MHV-A59的致病性是未知的。我们利用鼠巨噬细胞和C57 BL/6小鼠鼻内感染模型来解决这个问题。在原代巨噬细胞中，铁凋亡抑制剂抑制病毒繁殖、炎性细胞因子释放和MHV-A59感染后形成的细胞合胞体。在小鼠模型中，我们发现体内施用livestatin-1改善了由MHV-A59感染引起的肺部炎症和组织损伤。为了发现MHV-A59感染如何影响铁凋亡相关基因的表达，我们在原代巨噬细胞中进行了RNA-seq，发现MHV-A59感染上调了酰基辅酶A合成酶长链家族成员1（ACSL 1）的表达，ACSL 1是一种新型的铁凋亡诱导剂。使用铁凋亡抑制剂和TLR 4抑制剂，我们发现MHV-A59导致NF-κ B依赖性，TLR 4非依赖性ACSL 1上调。因此，ACSL 1抑制剂Triacsin C抑制MHV-A59感染诱导的合胞体形成和原代巨噬细胞中的病毒繁殖。总的来说，我们的研究表明，铁凋亡抑制保护宿主免受MHV-A59感染。靶向铁凋亡可能作为一种潜在的治疗方法，用于处理冠状病毒感染引起的过度炎症。
Murine hepatitis virus strain A59 (MHV-A59) was shown to induce pyroptosis, apoptosis, and necroptosis of infected cells, especially in the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59 is unknown. We utilized murine macrophages and a C57BL/6 mice intranasal infection model to address this. In primary macrophages, the ferroptosis inhibitor inhibited viral propagation, inflammatory cytokines released, and cell syncytia formed after MHV-A59 infection. In the mouse model, we found that in vivo administration of liproxstatin-1 ameliorated lung inflammation and tissue injuries caused by MHV-A59 infection. To find how MHV-A59 infection influenced the expression of ferroptosis-related genes, we performed RNA-seq in primary macrophages and found that MHV-A59 infection upregulates the expression of the acyl-CoA synthetase long-chain family member 1 (ACSL1), a novel ferroptosis inducer. Using ferroptosis inhibitors and a TLR4 inhibitor, we showed that MHV-A59 resulted in the NF-kB-dependent, TLR4-independent ACSL1 upregulation. Accordingly, ACSL1 inhibitor Triacsin C suppressed MHV-A59-infection-induced syncytia formation and viral propagation in primary macrophages. Collectively, our study indicates that ferroptosis inhibition protects hosts from MHV-A59 infection. Targeting ferroptosis may serve as a potential treatment approach for dealing with hyper-inflammation induced by coronavirus infection.
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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
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：
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：
3.6
作者：
Girelli D;Marchi G;Busti F;Vianello A
通讯作者：
Vianello A
影响因子：
64.5
作者：
Daniloski Z;Jordan TX;Wessels HH;Hoagland DA;Kasela S;Legut M;Maniatis S;Mimitou EP;Lu L;Geller E;Danziger O;Rosenberg BR;Phatnani H;Smibert P;Lappalainen T;tenOever BR;Sanjana NE
通讯作者：
Sanjana NE