Multi-platform omics analysis of Nipah virus infection reveals viral glycoprotein modulation of mitochondria

尼帕病毒感染的多平台组学分析揭示了病毒糖蛋白对线粒体的调控作用

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作者:Gunner P Johnston ,Fikret Aydemir ,Haewon Byun ,Emmie de Wit ,Kristie L Oxford ,Jennifer E Kyle ,Jason E McDermott ,Brooke L Deatherage Kaiser ,Cameron P Casey ,Karl K Weitz ,Heather M Olson ,Kelly G Stratton ,Natalie C Heller ,Viraj Upadhye ,I Abrrey Monreal ,J Lizbeth Reyes Zamora ,Lei Wu ,D H Goodall ,David W Buchholz ,Joeva J Barrow ,Katrina M Waters ,Ruth N Collins ,Heinz Feldmann ,Joshua N Adkins ,Hector C Aguilar

Abstract

The recent global pandemic illustrates the importance of understanding the host cellular infection processes of emerging zoonotic viruses. Nipah virus (NiV) is a deadly zoonotic biosafety level 4 encephalitic and respiratory paramyxovirus. Our knowledge of the molecular cell biology of NiV infection is extremely limited. This study identified changes in cellular components during NiV infection of human cells using a multi-platform, high-throughput transcriptomics, proteomics, lipidomics, and metabolomics approach. Remarkably, validation via multi-disciplinary approaches implicated viral glycoproteins in enriching mitochondria-associated proteins despite an overall decrease in protein translation. Our approach also allowed the mapping of significant fluctuations in the metabolism of glucose, lipids, and several amino acids, suggesting periodic changes in glycolysis and a transition to fatty acid oxidation and glutamine anaplerosis to support mitochondrial ATP synthesis. Notably, these analyses provide an atlas of cellular changes during NiV infections, which is helpful in designing therapeutics against the rapidly growing Henipavirus genus and related viral infections.

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