FROM NIPAH VIRUS HOST INFECTION TO THE PRODUCTION OF NEW VIRAL PARTICLES

dc.contributor.authorJohnston, Gunner Pete
dc.contributor.chairAguilar-Carreno, Hector
dc.contributor.committeeMemberWhittaker, Gary R.
dc.contributor.committeeMemberCollins, Ruth N.
dc.contributor.committeeMemberVogt, Volker M.
dc.date.accessioned2019-10-15T15:31:39Z
dc.date.available2021-06-05T06:00:49Z
dc.date.issued2019-05-30
dc.descriptionSupplemental file(s) description: Tables 4.1 and 4.2
dc.description.abstractNipah virus (NiV) belongs to the viral family Paramyxoviridae and is a pathogen of significant threat to global human health and agriculture. The absence of approved vaccines or treatments for NiV, severe human mortality reaching 100% rates in recent outbreaks, and the identification of at least twenty related viruses, underlines the urgency with which NiV and related pathogens should be studied. Despite prior reports that the NiV matrix (M) protein is the only viral protein significantly involved in particle formation and budding, we report that the NiV fusion (F) protein supports budding by enriching incorporation of the NiV attachment (G) protein into particles. Further, we report that this novel function of NiV F is dependent on motifs within its cytoplasmic tail, indicating potential dependence on cellular machinery. These findings were expanded upon with isolation of viral particles produced from different combinations of F, G, and M and subsequent proteomic analysis of such particles. These analyses and validation identified F-driven budding as most associated with cellular machinery, particularly vesicular trafficking and the actin cytoskeleton. Cellular factors involved in regulating endocytosis and recycling as well as ESCRTs were highly modulatory of F budding whether F was expressed alone or co-expressed with G and M. Finally, by broadening our use of high-throughput and bioinformatic technologies to “live” NiV infection at bio-safety level 4 conditions, we describe a novel study offering a comprehensive overview of infection. This multi-omics approach, combining transcriptomics, proteomics, metabolomics, and lipidomics indicated drastic changes to human cells affecting major processes including immune response, metabolism, and gene expression. Interestingly, we report substantial decreases in the abundance of proteins involved in translation, however, proteins associated with numerous, specific processes such as RNA processing exhibited dramatic enrichment. Interestingly, we also report major discrepancies between transcriptomics and proteomics, suggesting probable regulation of post-transcriptional protein expression during infection. Metabolic and lipidomic profiles supported shunting of glucose into nucleotide synthesis, the use of glutamine in anaplerosis, and the use of triglyceride catabolism to support cellular function. These findings have not been reported before for a henipavirus infection, begging further studies into their importance to infection.
dc.identifier.doihttps://doi.org/10.7298/2xhm-z789
dc.identifier.otherJohnston_cornellgrad_0058F_11402
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:11402
dc.identifier.otherbibid: 11050405
dc.identifier.urihttps://hdl.handle.net/1813/67423
dc.language.isoen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjecttranscriptomics
dc.subjectproteomics
dc.subjectCellular biology
dc.subjectBioinformatics
dc.subjectVirology
dc.subjectAssembly
dc.subjectBudding
dc.subjectNipah
dc.subjectParamyxovirus
dc.titleFROM NIPAH VIRUS HOST INFECTION TO THE PRODUCTION OF NEW VIRAL PARTICLES
dc.typedissertation or thesis
dcterms.licensehttps://hdl.handle.net/1813/59810
thesis.degree.disciplineBiomedical and Biological Sciences
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh.D., Biomedical and Biological Sciences
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