title: Characterization of the host response to pichinde virus infection in the Syrian golden hamster by species-specific kinome analysis.
abstract: The Syrian golden hamster has been increasingly used to study viral hemorrhagic fever (VHF) pathogenesis and countermeasure efficacy. As VHFs are a global health concern, well-characterized animal models are essential for both the development of therapeutics and vaccines as well as for increasing our understanding of the molecular events that underlie viral pathogenesis. However, the paucity of reagents or platforms that are available for studying hamsters at a molecular level limits the ability to extract biological information from this important animal model. As such, there is a need to develop platforms/technologies for characterizing host responses of hamsters at a molecular level. To this end, we developed hamster-specific kinome peptide arrays to characterize the molecular host response of the Syrian golden hamster. After validating the functionality of the arrays using immune agonists of defined signaling mechanisms (lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α), we characterized the host response in a hamster model of VHF based on Pichinde virus (PICV(1)) infection by performing temporal kinome analysis of lung tissue. Our analysis revealed key roles for vascular endothelial growth factor (VEGF), interleukin (IL) responses, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and Toll-like receptor (TLR) signaling in the response to PICV infection. These findings were validated through phosphorylation-specific Western blot analysis. Overall, we have demonstrated that hamster-specific kinome arrays are a robust tool for characterizing the species-specific molecular host response in a VHF model. Further, our results provide key insights into the hamster host response to PICV infection and will inform future studies with high-consequence VHF pathogens.
authors.affiliation: From the ‡Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA;
authors.forename: Shane
authors.initials: S
authors.lastname: Falcinelli
authors.affiliation: §Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, USA;
authors.forename: Brian B
authors.initials: BB
authors.lastname: Gowen
authors.affiliation: ¶Department of Computer Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada;
authors.forename: Brett
authors.initials: B
authors.lastname: Trost
authors.affiliation: ‡‡Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada, ‖Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada;
authors.forename: Scott
authors.initials: S
authors.lastname: Napper
authors.affiliation: ¶Department of Computer Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada;
authors.forename: Anthony
authors.initials: A
authors.lastname: Kusalik
authors.affiliation: From the ‡Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA;
authors.forename: Reed F
authors.initials: RF
authors.lastname: Johnson
authors.affiliation: **Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA;
authors.forename: David
authors.initials: D
authors.lastname: Safronetz
authors.affiliation: **Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA;
authors.forename: Joseph
authors.initials: J
authors.lastname: Prescott
authors.affiliation: §§Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA; ¶¶National Biodefense Analysis and Countermeasures Center, Frederick, MD 21702, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Wahl-Jensen
authors.affiliation: From the ‡Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA; §§Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA;
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.affiliation: §§Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA; kindrachuk.kenneth@nih.gov.
authors.forename: Jason
authors.initials: J
authors.lastname: Kindrachuk
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006478:Hemorrhagic Fever, American / Q000201:enzymology / Q000821:virology*; D007378:Interleukins / Q000302:isolation & purification; D008168:Lung / Q000201:enzymology* / Q000821:virology; D008647:Mesocricetus; D016328:NF-kappa B / Q000302:isolation & purification; D010766:Phosphorylation; D018052:Pichinde virus / Q000502:physiology*; D011494:Protein Kinases / Q000302:isolation & purification*; D020543:Proteome / Q000032:analysis*; D015398:Signal Transduction; D013045:Species Specificity; D051193:Toll-Like Receptors / Q000302:isolation & purification; D042461:Vascular Endothelial Growth Factor A / Q000302:isolation & purification
chemical_list: D007378:Interleukins; D016328:NF-kappa B; D020543:Proteome; D051193:Toll-Like Receptors; D042461:Vascular Endothelial Growth Factor A; D011494:Protein Kinases