Infection-Induced Peroxisome Biogenesis Is a Metabolic Strategy for Herpesvirus Replication.
Infection-Induced Peroxisome Biogenesis Is a Metabolic Strategy for Herpesvirus Replication.
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DOI：
10.1016/j.chom.2018.09.002
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发表时间：
2018-10-10
影响因子：
30.3
通讯作者：
Cristea IM
中科院分区：
文献类型：
--
作者：
Jean Beltran PM;Cook KC;Hashimoto Y;Galitzine C;Murray LA;Vitek O;Cristea IM
病毒蛋白已经进化到靶向细胞器并篡夺其功能以进行病毒复制。尽管对几种细胞器的这些关键功能有所了解，但对感染过程中的过氧化物酶体知之甚少。过氧化物酶体是主要的代谢细胞器，在脂质代谢中具有重要功能。在这里，我们发现包膜病毒人类巨细胞病毒（HCMV）和单纯疱疹病毒（HSV-1）诱导过氧化物酶体的生物发生和独特的形态变化，以支持它们的复制。靶向蛋白质组学定量揭示了全球病毒诱导的过氧化物酶体蛋白上调。数学模型和显微镜结构分析表明，感染触发过氧化物酶体生长和裂变，导致过氧化物酶体数量增加和不规则的圆盘状结构。hcmv诱导的过氧化物酶体生物发生增加了磷脂浆磷脂原，从而增强了病毒的产生。对于非包膜腺病毒，没有观察到过氧化物酶体的调节和依赖性。我们的发现揭示了过氧化物酶体在病毒发病机制中的作用，可能对多重包膜病毒有影响。Jean Beltran等人揭示了病毒诱导的过氧化物酶体功能调节以促进病毒复制，这一机制可能与包膜病毒有关。人巨细胞病毒增加过氧化物酶体数量和蛋白质组丰度，并改变过氧化物酶体形状。这代表了一种病毒参与过氧化物酶体脂质代谢以组装感染性颗粒的策略。
Viral proteins have evolved to target cellular organelles and usurp their functions for virus replication. Despite the knowledge of these critical functions for several organelles, little is known about peroxisomes during infection. Peroxisomes are primarily metabolic organelles with important functions in lipid metabolism. Here, we discovered that the enveloped viruses human cytomegalovirus (HCMV) and herpes simplex virus (HSV-1) induce the biogenesis of and unique morphological changes to peroxisomes to support their replication. Targeted proteomic quantification revealed a global virus-induced upregulation of peroxisomal proteins. Mathematical modeling and microscopy structural analysis show that infection triggers peroxisome growth and fission, leading to increased peroxisome numbers and irregular disc-like structures. HCMV-induced peroxisome biogenesis increased the phospholipid plasmalogen, thereby enhancing virus production. Peroxisome regulation and dependence were not observed for the non-enveloped adenovirus. Our findings uncover a role of peroxisomes in viral pathogenesis, with likely implications for multiple enveloped viruses. Jean Beltran et al. reveal the virus-induced modulation of peroxisome functions to facilitate viral replication, a mechanism likely relevant across enveloped viruses. Human cytomegalovirus increases peroxisome numbers and proteome abundance, and alters peroxisome shape. This represents a virus strategy to engage peroxisome lipid metabolism for the assembly of infectious particles.
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影响因子：
14.9
作者：
Deutsch EW;Csordas A;Sun Z;Jarnuczak A;Perez-Riverol Y;Ternent T;Campbell DS;Bernal-Llinares M;Okuda S;Kawano S;Moritz RL;Carver JJ;Wang M;Ishihama Y;Bandeira N;Hermjakob H;Vizcaíno JA
通讯作者：
Vizcaíno JA
影响因子：
64.5
作者：
Dixit E;Boulant S;Zhang Y;Lee AS;Odendall C;Shum B;Hacohen N;Chen ZJ;Whelan SP;Fransen M;Nibert ML;Superti-Furga G;Kagan JC
通讯作者：
Kagan JC
影响因子：
5.3
作者：
Li, XL;Baumgart, E;Gould, SJ
通讯作者：
Gould, SJ
影响因子：
5.4
作者：
Chahal, Jasdave S.;Flint, S. J.
通讯作者：
Flint, S. J.
影响因子：
4.6
作者：
Magalhães AC;Ferreira AR;Gomes S;Vieira M;Gouveia A;Valença I;Islinger M;Nascimento R;Schrader M;Kagan JC;Ribeiro D
通讯作者：
Ribeiro D