About: Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis
Creator	Baric, Ralph Jensen, Kara Leist, Sarah Sheahan Id, Timothy
source	Medline; PMC
abstract	Newly emerging viral pathogens pose a constant and unpredictable threat to human and animal health. Coronaviruses (CoVs) have a penchant for sudden emergence, as evidenced by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and most recently, swine acute diarrhea syndrome coronavirus (SADS-CoV). Small animal models of emerging viral pathogenesis are crucial to better understand the virus and host factors driving disease progression. However, rodent models are often criticized for their limited translatability to humans. The complete blood count is the most ordered clinical test in the United States serving as the cornerstone of clinical medicine and differential diagnosis. We recently generated a mouse model for MERS-CoV pathogenesis through the humanization of the orthologous entry receptor dipeptidyl peptidase 4 (DPP4). To increase the translatability of this model, we validated and established the use of an automated veterinary hematology analyzer (VetScan HM5) at biosafety level 3 for analysis of peripheral blood. MERS-CoV lung titer peaked 2 days post infection concurrent with lymphopenia and neutrophilia in peripheral blood, two phenomena also observed in MERS-CoV infection of humans. The fluctuations in leukocyte populations measured by Vetscan HM5 were corroborated by standard flow cytometry, thus confirming the utility of this approach. Comparing a sublethal and lethal dose of MERS-CoV in mice, analysis of daily blood draws demonstrates a dose dependent modulation of leukocytes. Major leukocyte populations were modulated before weight loss was observed. Importantly, neutrophil counts on 1dpi were predictive of disease severity with a lethal dose of MERS-CoV highlighting the predictive value of hematology in this model. Taken together, the inclusion of hematological measures in mouse models of emerging viral pathogenesis increases their translatability and should elevate the preclinical evaluation of MERS-CoV therapeutics and vaccines to better mirror the complexity of the human condition.
has issue date	2019-07-24(xsd:dateTime)
bibo:doi	10.1371/journal.pone.0220126
bibo:pmid	31339932
has license	cc-by
sha1sum (hex)	c66b53fa3a31eb9fcc20c56830c89061b7caed49
schema:url	https://doi.org/10.1371/journal.pone.0220126
resource representing a document's title	Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis
has PubMed Central identifier	PMC6655769
has PubMed identifier	31339932
schema:publication	PLoS One
resource representing a document's body	covid:c66b53fa3a31eb9fcc20c56830c89061b7caed49#body_text
is schema:about of	named entity 'HEMATOLOGICAL' named entity 'expressed' named entity 'mouse' named entity 'draws' named entity 'infected' named entity 'represent' named entity 'lethal dose' named entity 'standard' named entity 'determined' named entity 'leukocyte' named entity 'measures' named entity 'peptidase' named entity 'MERS-CoV' named entity 'standard deviation' named entity 'represent' named entity 'MOUSE MODELS' named entity 'TRANSLATION' named entity 'FLOW CYTOMETRY' named entity 'LUNG' named entity 'HUMAN' named entity 'ANIMALS' named entity 'EXPECTED' named entity 'PRECLINICAL' named entity 'DAYS' named entity 'PHENOMENA' named entity 'LINE' named entity 'MEASURES' named entity 'LIMITED' named entity 'PEAKED' named entity 'PREDICTIVE' named entity 'WEIGHT LOSS' named entity 'MOUSE' named entity 'EVALUATION' named entity 'EMERGENCE' named entity 'PATHOGENESIS' named entity 'KINETIC' named entity 'EXPERIMENTS' named entity 'FREQUENCIES' named entity 'CONSTANT' named entity 'INCLUSION' named entity 'RODENT' named entity 'MICE' named entity 'STANDARD ERROR OF THE MEAN' named entity 'GENERATED' named entity 'TO INCREASE' named entity 'REPRESENT' named entity 'DIPEPTIDYL PEPTIDASE 4' named entity 'MERS-COV' named entity 'HEMATOLOGY' named entity '28A' named entity 'WEIGHT' named entity 'DIFFERENTIAL DIAGNOSIS' named entity 'TAKEN' named entity 'ANALYSIS' named entity 'VACCINES' named entity 'MODEL' named entity 'MODELS' named entity 'BLOOD DRAWS' named entity 'ELEVATE' named entity 'WHITE BLOOD CELLS' named entity 'SMALL ANIMAL' named entity 'COMPLEXITY' named entity 'HIGHLIGHTING' named entity 'NEUTROPHILS' named entity 'COMPLETE BLOOD COUNT' named entity 'POPULATIONS' named entity 'VIRAL PATHOGENESIS' named entity 'SERVING' named entity 'SINGLE' named entity 'BIOSAFETY LEVEL 3' named entity 'NEUTROPHIL' named entity 'INCREASING' named entity 'MERS CORONAVIRUS' named entity 'ANALYSIS' named entity 'DOTTED' named entity 'CLINICAL MEDICINE' named entity 'BETTER' named entity 'ESTABLISHED'

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