Acyl-Coa Thioesterases: A Rheostat That Controls Activated Fatty Acids Modulates Dengue Virus Serotype 2 Replication.
Acyl-Coa Thioesterases: A Rheostat That Controls Activated Fatty Acids Modulates Dengue Virus Serotype 2 Replication.
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DOI：
10.3390/v14020240
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发表时间：
2022-01-25
期刊：
影响因子：
--
通讯作者：
Perera R
中科院分区：
文献类型：
--
作者：
St Clair LA;Mills SA;Lian E;Soma PS;Nag A;Montgomery C;Ramirez G;Chotiwan N;Gullberg RC;Perera R
在登革热病毒（DENV）感染期间，宿主细胞内的脂质景观显著改变以组装支持病毒复制和颗粒组装的膜平台。脂酰辅酶A是形成这些膜的复合脂质的生物合成中的关键中间体。它们也作为细胞中的关键信号脂质发挥作用。在这里，我们对酰基辅酶A硫酯酶（ACOT）进行了功能丧失研究，这是一种将脂肪酰基辅酶A水解为游离脂肪酸和辅酶A的酶家族，以了解它们对DENV生命周期的影响。I型ACOT 1（细胞质）和2（线粒体）的功能丧失一起显著增加了DENV血清型2（DENV 2）病毒复制和感染性颗粒释放。然而，线粒体ACOT2的单独敲低显著降低了DENV 2蛋白翻译、基因组复制和感染性病毒释放。此外，线粒体II型ACOT的ACOT 7功能的丧失也类似地抑制了DENV 2。由于ACOT1和ACOT2是剪接变体，因此这些数据表明，由于这些蛋白质的位置（分别为细胞溶质和线粒体）而导致的功能差异和底物特异性可能是DENV 2感染表型差异的原因。此外，线粒体ACOT2和ACOT7表达的丧失也改变了位于细胞内多个细胞器区室中的几种ACOT的表达，突出了DENV 2病毒生命周期中ACOT之间的复杂关系。
During infection with dengue viruses (DENVs), the lipid landscape within host cells is significantly altered to assemble membrane platforms that support viral replication and particle assembly. Fatty acyl-CoAs are key intermediates in the biosynthesis of complex lipids that form these membranes. They also function as key signaling lipids in the cell. Here, we carried out loss of function studies on acyl-CoA thioesterases (ACOTs), a family of enzymes that hydrolyze fatty acyl-CoAs to free fatty acids and coenzyme A, to understand their influence on the lifecycle of DENVs. The loss of function of the type I ACOTs 1 (cytoplasmic) and 2 (mitochondrial) together significantly increased DENV serotype 2 (DENV2) viral replication and infectious particle release. However, isolated knockdown of mitochondrial ACOT2 significantly decreased DENV2 protein translation, genome replication, and infectious virus release. Furthermore, loss of ACOT7 function, a mitochondrial type II ACOT, similarly suppressed DENV2. As ACOT1 and ACOT2 are splice variants, these data suggest that functional differences and substrate specificities due to the location (cytosol and mitochondria, respectively) of these proteins may account for the differences in DENV2 infection phenotype. Additionally, loss of mitochondrial ACOT2 and ACOT7 expression also altered the expression of several ACOTs located in multiple organelle compartments within the cell, highlighting a complex relationship between ACOTs in the DENV2 virus lifecycle.
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影响因子：
6.7
作者：
Chotiwan N;Andre BG;Sanchez-Vargas I;Islam MN;Grabowski JM;Hopf-Jannasch A;Gough E;Nakayasu E;Blair CD;Belisle JT;Hill CA;Kuhn RJ;Perera R
通讯作者：
Perera R
通过PPARα/PGC1α信号传导，酰基辅酶A硫酯酶1对糖尿病心脏的保护作用。
影响因子：
3.7
作者：
Yang S;Chen C;Wang H;Rao X;Wang F;Duan Q;Chen F;Long G;Gong W;Zou MH;Wang DW
通讯作者：
Wang DW
影响因子：
4.8
作者：
Bekeova, Carmen;Anderson-Pullinger, Lauren;Seifert, Erin L.
通讯作者：
Seifert, Erin L.
影响因子：
4.8
作者：
Hunt, Mary C.;Rautanen, Anna;Alexson, Stefan E. H.
通讯作者：
Alexson, Stefan E. H.
影响因子：
5.3
作者：
Ellis, Jessica M.;Wong, William;Wolfgang, Michael J.
通讯作者：
Wolfgang, Michael J.