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Effect of the ribonuclease binase on the proteome of A549 cell infected by influenza A(H1N1pdm09) virus

ABSTRACT: Ribonucleases (RNases) of different origin demonstrate antiviral effects that are mediated by the direct RNase action on RNA species and can also involve signal transduction modulation. To reveal cellular targets and explain the mechanisms underlying the antiviral effect employed by the small extra-cellular ribonuclease of Bacillus pumilus (binase) both in vitro and in vivo, a shotgun proteomic analysis of influenza A virus (H1N1pdm09)-infected A549 cells upon binase treatment, was performed.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Raihan Shah Mahmud

PROVIDER: PXD013545 | JPOST Repository | Thu Apr 18 00:00:00 BST 2019

REPOSITORIES: jPOST

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			Action	DRS
	Raich_1_Kontr_RA3_01_1760.baf	Other
	Raich_1_Kontr_RA3_01_1760.mgf	Mgf
	Raich_1_Kontr_RA3_01_1760.mzid	Mzid
	Raich_2_kl_RNAse_RA4_01_1762.baf	Other
	Raich_2_kl_RNAse_RA4_01_1762.mgf	Mgf

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Project description:The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5M-bM-^@M-^Y triphosphate (5M-bM-^@M-^Yppp) terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5M-bM-^@M-^YpppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, andinduction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN)signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5M-bM-^@M-^YpppRNA, and not by IFNM-NM-1-2bthat included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5M-bM-^@M-^YpppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5M-bM-^@M-^YpppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach providestranscriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5M-bM-^@M-^YpppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents. Kinetic analysis of A549 cells treated with 5'pppRNA and analyzed at 1h, 2h, 4h, 6h, 8h, 12h, 24h or 48h.

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Effect of the ribonuclease binase on the proteome of A549 cell infected by influenza A(H1N1pdm09) virus

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