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
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, USA.
Cell Rep. 2025 Mar 25;44(3):115411. doi: 10.1016/j.celrep.2025.115411. Epub 2025 Mar 17.
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.
近期的全球大流行说明了了解新出现的人畜共患病毒的宿主细胞感染过程的重要性。尼帕病毒（NiV）是一种致命的人畜共患生物安全4级脑炎和呼吸道副粘病毒。我们对NiV感染的分子细胞生物学的了解极为有限。本研究采用多平台、高通量转录组学、蛋白质组学、脂质组学和代谢组学方法，确定了人类细胞在NiV感染过程中细胞成分的变化。值得注意的是，尽管蛋白质翻译总体下降，但通过多学科方法进行的验证表明病毒糖蛋白与线粒体相关蛋白的富集有关。我们的方法还能够绘制出葡萄糖、脂质和几种氨基酸代谢的显著波动情况，这表明糖酵解存在周期性变化，并向脂肪酸氧化和谷氨酰胺回补转变以支持线粒体ATP合成。值得注意的是，这些分析提供了NiV感染期间细胞变化的图谱，这有助于设计针对快速增长的亨尼帕病毒属及相关病毒感染的治疗方法。
