About: Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus

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About: Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus Goto Sponge NotDistinct Permalink

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus
Creator	Takeda, Makoto Sato, Hironori Fukushi, Shuetsu Nagata, Noriyo Okamura, Tadashi Tashiro, Masato Hasegawa, Hideki Iwata-Yoshikawa, Naoko Kotani, Osamu Sato, Yuko Sekimukai, Hanako Shimizu, Yukiko Suzuki, Tadaki Iwata-Yoshikawa N, Citation Sato, Suzuki
topic	covid:27c24bc25e5f22f0771e1fcb3276c728fb446828#this
Source	Medline; PMC
abstract	Middle East respiratory syndrome coronavirus (MERS-CoV) infection can manifest as a mild illness, acute respiratory distress, organ failure, or death. Several animal models have been established to study disease pathogenesis and to develop vaccines and therapeutic agents. Here, we developed transgenic (Tg) mice on a C57BL/6 background; these mice expressed human CD26/dipeptidyl peptidase 4 (hDPP4), a functional receptor for MERS-CoV, under the control of an endogenous hDPP4 promoter. We then characterized this mouse model of MERS-CoV. The expression profile of hDPP4 in these mice was almost equivalent to that in human tissues, including kidney and lung; however, hDPP4 was overexpressed in murine CD3-positive cells within peripheral blood and lymphoid tissues. Intranasal inoculation of young and adult Tg mice with MERS-CoV led to infection of the lower respiratory tract and pathological evidence of acute multifocal interstitial pneumonia within 7 days, with only transient loss of body weight. However, the immunopathology in young and adult Tg mice was different. On day 5 or 7 postinoculation, lungs of adult Tg mice contained higher levels of proinflammatory cytokines and chemokines associated with migration of macrophages. These results suggest that the immunopathology of MERS-CoV infection in the Tg mouse is age dependent. The mouse model described here will increase our understanding of disease pathogenesis and host mediators that protect against MERS-CoV infection. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) infections are endemic in the Middle East and a threat to public health worldwide. Rodents are not susceptible to the virus because they do not express functional receptors; therefore, we generated a new animal model of MERS-CoV infection based on transgenic mice expressing human DPP4 (hDPP4). The pattern of hDPP4 expression in this model was similar to that in human tissues (except lymphoid tissue). In addition, MERS-CoV was limited to the respiratory tract. Here, we focused on host factors involved in immunopathology in MERS-CoV infection and clarified differences in antiviral immune responses between young and adult transgenic mice. This new small-animal model could contribute to more in-depth study of the pathology of MERS-CoV infection and aid development of suitable treatments.
has issue date	2019-01-09(xsd:dateTime)
bibo:doi	10.1128/jvi.01818-18
bibo:pmid	30626685
has license	bronze-oa
sha1sum (hex)	27c24bc25e5f22f0771e1fcb3276c728fb446828
schema:url	https://doi.org/10.1128/jvi.01818-18
resource representing a document's title	Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus
has PubMed Central identifier	PMC6401458
has PubMed identifier	30626685
schema:publication	Journal of Virology
resource representing a document's body	covid:27c24bc25e5f22f0771e1fcb3276c728fb446828#body_text
is http://vocab.deri.ie/void#inDataset of	proxy:http/ns.inria.fr/covid19/27c24bc25e5f22f0771e1fcb3276c728fb446828
is schema:about of	named entity 'MERS-CoV' named entity 'study' named entity 'promoter' named entity 'human' named entity 'acute' named entity 'infection' named entity 'inoculation' named entity 'therapeutic' named entity 'transient' named entity 'lymphoid tissue' named entity 'macrophages' named entity 'age' named entity 'host' named entity 'Acute Respiratory Infection' covid:arg/27c24bc25e5f22f0771e1fcb3276c728fb446828 named entity 'loss' named entity 'clarified' named entity 'body weight' named entity 'infection' named entity 'cells' named entity 'based' named entity 'MERS-CoV' named entity 'coronavirus' named entity 'express' named entity 'MERS-CoV' named entity 'acute' named entity 'respiratory tract' named entity 'tissues' named entity 'expression profile' named entity 'factors' named entity 'addition' named entity 'higher' named entity 'adult' named entity 'endemic' named entity 'These' named entity 'immunopathology' named entity 'immune responses' named entity 'Peptidase' named entity 'DPP4' named entity 'mice' named entity 'CD26' named entity 'mouse model' named entity 'kidney' named entity 'MERS-CoV' named entity 'immune responses' named entity 'transgenic' named entity 'inoculation' named entity 'proinflammatory cytokines' named entity 'infection' named entity 'MERS-CoV' named entity 'antiviral' named entity 'immunopathology' named entity 'lungs' named entity 'public health' named entity 'MERS-CoV' named entity 'Dipeptidyl Peptidase 4' named entity 'adult' named entity 'This' named entity 'CD3' named entity 'reverse transcription' named entity 'liver' named entity 'gene' named entity 'human tissues' named entity 'infection' named entity 'murine'

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