Starvation after infection restricts enterovirus D68 replication.
Starvation after infection restricts enterovirus D68 replication.
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DOI：
10.1080/15548627.2022.2062888
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发表时间：
2023-01
期刊：
影响因子：
13.3
通讯作者：
Jackson, William T.
中科院分区：
文献类型：
--
作者：
Jassey, Alagie;Wagner, Michael A.;Galitska, Ganna;Paudel, Bimal;Miller, Katelyn;Jackson, William T.
肠道病毒D68(EV-D68)是一种与急性弛缓性脊髓炎有关的呼吸道病原体，急性弛缓性脊髓炎是一种儿童麻痹疾病。目前还没有获得批准的针对EV-D68的疫苗或抗病毒治疗。感染这种病毒会导致自噬小体的形成，以促进其复制，但会阻止下游的自噬小体-溶酶体融合步骤。在这里，我们研究了通过饥饿诱导自噬的影响，无论是在感染前饥饿之前(SBI)还是在感染后饥饿(SAI)EV-D68感染之后。我们发现SAI，而不是SBI，可以减弱EV-D68在多个细胞系中的复制，并取消病毒介导的宿主自噬通量相关蛋白的切割。此外，SAI在EV-D68复制过程中诱导了自噬通量，并阻止了微小核糖核酸病毒复制所需的病毒诱导膜的产生。药物抑制SAI期间的自噬通量并不能挽救EV-D68滴度。SAI在多种细胞类型中都有相同的作用，并限制了几种医学上相关的小核糖核酸病毒的复制。我们的结果强调了自噬小体对小核糖核酸病毒复制的重要性，并确定SAI是一种有吸引力的广谱抗小核糖核酸病毒策略。缩写：BaF：巴菲尔霉素A1；CCCP：间氯苯肼；CQ：氯喹；CVB3：柯萨奇病毒B3；EV-D68：肠道病毒D68；HPI：感染后1小时；MAP1LC3/LC3：微管相关蛋白1轻链3；MOI：感染的多样性；NSP2B：非结构蛋白2B；PV：脊髓灰质炎病毒；RES：白藜芦醇；RV14：鼻病毒14；SAI：感染后饥饿；SBI：感染前饥饿；SNAP29：突触体相关蛋白29；SQSTM1/p62：隔离体1；TFEB：转录因子EB。
Enterovirus D68 (EV-D68) is a respiratory pathogen associated with acute flaccid myelitis, a childhood paralysis disease. No approved vaccine or antiviral treatment exists against EV-D68. Infection with this virus induces the formation of autophagosomes to enhance its replication but blocks the downstream autophagosome- lysosome fusion steps. Here, we examined the impact of autophagy induction through starvation, either before (starvation before infection, SBI) or after (starvation after infection, SAI) EV-D68 infection. We showed that SAI, but not SBI, attenuated EV-D68 replication in multiple cell lines and abrogated the viral-mediated cleavage of host autophagic flux-related proteins. Furthermore, SAI induced autophagic flux during EV-D68 replication and prevented production of virus-induced membranes, which are required for picornavirus replication. Pharmacological inhibition of autophagic flux during SAI did not rescue EV-D68 titers. SAI had the same effect in multiple cell types, and restricted the replication of several medically relevant picornaviruses. Our results highlight the significance of autophagosomes for picornavirus replication and identify SAI as an attractive broad-spectrum anti-picornavirus strategy. Abbreviations: BAF: bafilomycin A1; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CQ: chloroquine; CVB3: coxsackievirus B3; EV-D68: enterovirus D68; hpi: hour post-infection; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; NSP2B: nonstructural protein 2B; PV: poliovirus; RES: resveratrol; RV14: rhinovirus 14; SAI: starvation after infection; SBI: starvation before infection; SNAP29: synaptosome associated protein 29; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB.
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影响因子：
5.9
作者：
Jackson, William T.
通讯作者：
Jackson, William T.
影响因子：
13.3
作者：
Brinck Andersen, Nanna-Sophie;Jorgensen, Sofie Eg;Mogensen, Trine H.
通讯作者：
Mogensen, Trine H.
DOI：
10.1083/jcb.201711002
发表时间：
2018-10-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mejlvang J;Olsvik H;Svenning S;Bruun JA;Abudu YP;Larsen KB;Brech A;Hansen TE;Brenne H;Hansen T;Stenmark H;Johansen T
通讯作者：
Johansen T
影响因子：
6.4
作者：
Brown DM;Hixon AM;Oldfield LM;Zhang Y;Novotny M;Wang W;Das SR;Shabman RS;Tyler KL;Scheuermann RH
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Scheuermann RH
影响因子：
6.4
作者：
Richards AL;Soares-Martins JA;Riddell GT;Jackson WT
通讯作者：
Jackson WT