Source:		PRJNA244298

     		Cytokine stimulation systems approach demonstrates
			differences in innate and pro-inflammatory
			host responses between genetically distinct
			MERS-CoV isolates.

			Michael G. Katze, Ph.D, Microbiology,
			University of Washington (Owner)

			Background: The recent emergence of a novel
			coronavirus in the Middle East (designated
			MERS-CoV) is a reminder of the zoonotic
			potential of coronaviruses and the severe
			disease these etiologic agents can cause
			in humans. Clinical features of
			Middle East respiratory syndrome (MERS)
			include severe acute pneumonia and renal failure
			that is highly reminiscent of
			severe acute respiratory syndrome (SARS)
			caused by SARS-CoV. The host response is
			a key component of highly pathogenic respiratory
			virus infection. Here, we computationally
			analyzed gene expression changes in a human
			airway epithelial cell line infected with
			two genetically distinct MERS-CoV strains obtained
			from human patients, MERS-CoV-EMC (designated
			EMC) and MERS-CoV-London (designated LoCoV).
			Results: Using topological techniques, such
			as persistence homology and filtered clustering,
			we characterized the host response system
			to the different MERS-CoVs, with LoCoV inducing
			early kinetic changes, between 3 and 12
			hours post infection, compared to EMC. Robust
			transcriptional changes distinguished the
			two MERS-CoV strains predominantly at the
			late time points. Combining statistical
			analysis of infection and cytokine-stimulated
			treatment transcriptomics, we identified
			differential innate and pro-inflammatory responses
			between the two virus strains, including
			up-regulation of extracellular remodeling
			genes following LoCoV infection and differential
			pro-inflammatory responses between the two
			strains. Conclusions: These transcriptional
			differences may be the result of amino acid
			differences in viral proteins known to modulate
			innate immunity against MERS infection.
			Overall design: Triplicate wells of Calu-3
			2B4 cells were infected with Human Coronavirus
			EMC 2012 (HCoV-EMC) or time-matched mock
			infected. Cells were harvested at 0, 3,
			7, 12, 18 and 24 hours post-infection (hpi),
			RNA extracted and transcriptomics analyzed
			by microarray.

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