SIRT-1 is required for release of enveloped enteroviruses.
SIRT-1 is required for release of enveloped enteroviruses.
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DOI：
10.7554/elife.87993
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发表时间：
2023-10-18
期刊：
影响因子：
7.7
通讯作者：
Jackson WT
中科院分区：
文献类型：
--
作者：
Jassey A;Logue J;Weston S;Wagner MA;Galitska G;Miller K;Frieman M;Jackson WT
肠道病毒D 68（EV-D 68）是一种重新出现的肠道病毒，可导致婴儿急性呼吸道疾病，最近被认为与急性弛缓性肌无力有关。在这里，我们表明组蛋白脱乙酰酶，SIRT-1，是必不可少的自噬和EV-D 68感染。SIRT-1的敲低抑制自噬并降低EV-D 68细胞外滴度。SIRT-1的前病毒活性不需要其脱乙酰酶活性或功能性自噬。我们证明，SIRT-1的前病毒活性是通过抑制内质网应激（ER应激）介导的。通过毒胡萝卜素处理或SIRT-1敲低细胞中的SERCA 2A敲低诱导ER应激对EV-D 68细胞外滴度没有额外的影响。SIRT-1的敲除也降低脊髓灰质炎病毒和SARS-CoV-2的滴度，但不降低柯萨奇病毒B3。在非裂解条件下，EV-D 68主要以包膜形式释放，该过程需要SIRT-1。我们的数据表明，SIRT-1，通过其易位到胞质溶胶，是至关重要的，以促进包膜EV-D 68病毒颗粒的释放。
Enterovirus D68 (EV-D68) is a re-emerging enterovirus that causes acute respiratory illness in infants and has recently been linked to Acute Flaccid Myelitis. Here, we show that the histone deacetylase, SIRT-1, is essential for autophagy and EV-D68 infection. Knockdown of SIRT-1 inhibits autophagy and reduces EV-D68 extracellular titers. The proviral activity of SIRT-1 does not require its deacetylase activity or functional autophagy. SIRT-1’s proviral activity is, we demonstrate, mediated through the repression of endoplasmic reticulum stress (ER stress). Inducing ER stress through thapsigargin treatment or SERCA2A knockdown in SIRT-1 knockdown cells had no additional effect on EV-D68 extracellular titers. Knockdown of SIRT-1 also decreases poliovirus and SARS-CoV-2 titers but not coxsackievirus B3. In non-lytic conditions, EV-D68 is primarily released in an enveloped form, and SIRT-1 is required for this process. Our data show that SIRT-1, through its translocation to the cytosol, is critical to promote the release of enveloped EV-D68 viral particles.
影响因子：
4
作者：
Singh P;Reza MI;Syed AA;Garg R;Husain A;Katekar R;Goand UK;Riyazuddin M;Gupta AP;Gayen JR
通讯作者：
Gayen JR