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

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...

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Published inCell reports (Cambridge) Vol. 44; no. 3; p. 115411
Main Authors Johnston, Gunner P., Aydemir, Fikret, Byun, Haewon, de Wit, Emmie, Oxford, Kristie L., Kyle, Jennifer E., McDermott, Jason E., Deatherage Kaiser, Brooke L., Casey, Cameron P., Weitz, Karl K., Olson, Heather M., Stratton, Kelly G., Heller, Natalie C., Upadhye, Viraj, Monreal, I. Abrrey, Reyes Zamora, J. Lizbeth, Wu, Lei, Goodall, D.H., Buchholz, David W., Barrow, Joeva J., Waters, Katrina M., Collins, Ruth N., Feldmann, Heinz, Adkins, Joshua N., Aguilar, Hector C.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 25.03.2025
Elsevier
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ISSN2211-1247
2211-1247
DOI10.1016/j.celrep.2025.115411

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Summary: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. [Display omitted] •This study identified cellular changes upon human cell infection by the deadly Nipah virus•We used a multi-platform transcriptomics, proteomics, lipidomics, and metabolomics approach•This study implicated mitochondria-associated protein enrichment and metabolic changes•These analyses provide an atlas of cellular changes that may help in designing therapeutics This study identified changes in cellular components that occur during infection of human cells by the deadly Nipah virus (NiV). We used a multi-platform, high-throughput transcriptomics, proteomics, lipidomics, and metabolomics approach, providing an atlas of cellular changes helpful in designing therapeutics against the rapidly growing and important Henipavirus genus.
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AC05-76RL01830; HSHQPM-14-X-00238; R01AI109022; DEAC05-76RLO1830
PNNL-SA-209082
National Institutes of Health (NIH)
USDOE Office of Science (SC), Biological and Environmental Research (BER)
US Department of Homeland Security (DHS)
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2025.115411