文献类型： 外文期刊

第一作者： Qiao, Yangyang

作者： Qiao, Yangyang;Wang, Zhitao;Han, Zhongxi;Shao, Yuhao;Ma, Yong;Liang, Yumeng;Chen, Zhijie;Wu, Hanguang;Cui, Lu;Zhang, Yanhui;Liu, Shengwang;Li, Hai;Wang, Zhitao;Chen, Zhijie

作者机构：

期刊名称：PLOS PATHOGENS （ 影响因子：6.823； 五年影响因子：7.455 ）

ISSN： 1553-7366

年卷期： 2020 年 16 卷 8 期

页码：

收录情况： SCI

摘要： Although therapeutics targeting viral metabolic processes have been considered as promising strategies to treat herpesvirus infection, the metabolic requirements of gallid alphaherpesvirus 1 (ILTV), which is economically important to the poultry industry worldwide, remain largely unknown. Using the ILTV-susceptible but nonpermissive chicken cell line DF-1 and the ILTV-permissive chicken cell line LMH as models, the present study explored the metabolic requirements of ILTV by global transcriptome analysis and metabolome assays of ILTV infected cell lines in combination with a set of functional validations. The extensive metabolic exploration demonstrated that ILTV infection tended to promote a metabolic shift from glycolysis to fatty acid (FA) and nucleotide biosynthesis and utilizes glutamine independently of glutaminolysis, without significant general effect on the TCA cycle. In addition, different metabolic pathways were found to be required for distinct stages of ILTV replication. Glucose and glutamine were required for the transcription of viral immediate early geneICP4and subsequent steps of viral replication. However, FA synthesis was essential for assembly but not required for other upstream steps of ILTV replication. Moreover, the metabolic requirements of ILTV infection revealed in chicken cell lines were further validated in chicken primary cells isolated from chicken embryo kidneys and chicken embryo livers. The present study, to the best of our knowledge, provides the first global metabolic profile of animal herpesviruses and illustrates the main characteristics of the metabolic program of ILTV. Author summary Virus-host metabolic interaction is a promising target for antiviral therapeutics. Explorations of viral-induced shifts of host metabolism could reveal substrates that are uniquely required at high levels for viral replication and have been conducted for many virus species in the last decade. Herpesviruses are commonly treated with nucleotide analogs in the clinic. However, recent metabolomics studies suggest that different herpesvirus species can execute distinct metabolic programs in host cells despite their high conservation of biological characteristics. To understand why herpesviruses have evolved to alter different metabolic processes in host cells and refine the antiviral treatments by targeting more species-specific metabolic requirements, metabolomic explorations of more herpesvirus species are needed. However, comprehensive exploration of virus-host metabolic interaction has only been limited to a few human herpesviruses. Gallid alphaherpesvirus 1 (ILTV), an economically important alphaherpesvirus to the poultry industry worldwide, is thought to be an ancient example of alphaherpesviruses. Here we reveal the global metabolic requirements of ILTV and highlight the common and unique metabolic characteristics of ILTV by comparing with the known global metabolic profiles of several human herpesviruses. Our study may increase current understanding of herpesvirus-host metabolic interplay and inspire further studies in this direction.

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