Dual RNA-Seq characterization of host and pathogen gene expression in liver cells infected with Crimean-Congo Hemorrhagic Fever Virus.

Autor: Kozak RA; Department of Laboratory Medicine & Molecular Diagnostics, Division of Microbiology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada., Fraser RS; Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada., Biondi MJ; Arthur Labatt Family School of Nursing, Western University, London, Ontario, Canada.; Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada., Majer A; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Medina SJ; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Griffin BD; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Kobasa D; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada., Stapleton PJ; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada., Urfano C; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Babuadze G; Infectious Diseases Research Centre, Université Laval, Quebec City, Quebec, Canada., Antonation K; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Fernando L; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Booth S; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Lillie BN; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada., Kobinger GP; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.; Infectious Diseases Research Centre, Université Laval, Quebec City, Quebec, Canada.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2020 Apr 06; Vol. 14 (4), pp. e0008105. Date of Electronic Publication: 2020 Apr 06 (Print Publication: 2020).
DOI: 10.1371/journal.pntd.0008105
Abstrakt: Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus that can cause a hemorrhagic fever in humans, with a case fatality rate of up to 40%. Cases of CCHFV have been reported in Africa, Asia, and southern Europe; and recently, due to the expanding range of its vector, autochthonous cases have been reported in Spain. Although it was discovered over 70 years ago, our understanding of the pathogenesis of this virus remains limited. We used RNA-Seq in two human liver cell lines (HepG2 and Huh7) infected with CCHFV (strain IbAr10200), to examine kinetic changes in host expression and viral replication simultaneously at 1 and 3 days post infection. Through this, numerous host pathways were identified that were modulated by the virus including: antiviral response and endothelial cell leakage. Notably, the genes encoding DDX60, a cytosolic component of the RIG-I signalling pathway and OAS2 were both shown to be dysregulated. Interestingly, PTPRR was induced in Huh7 cells but not HepG2 cells. This has been associated with the TLR9 signalling cascade, and polymorphisms in TLR9 have been associated with poor outcomes in patients. Additionally, we performed whole-genome sequencing on CCHFV to assess viral diversity over time, and its relationship to the host response. As a result, we have demonstrated that through next-generation mRNA deep-sequencing it is possible to not only examine mRNA gene expression, but also to examine viral quasispecies and typing of the infecting strain. This demonstrates a proof-of-principle that CCHFV specimens can be analyzed to identify both the virus and host biomarkers that may have implications for prognosis.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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