Adenovirus transduction to express human ACE2 causes obesity-specific morbidity in mice, impeding studies on the effect of host nutritional status on SARS-CoV-2 pathogenesis.
COVID-19
Diet-induced obesity
Pathology
Replication-defective adenovirus
Tissue
hACE2
Journal
Virology
ISSN: 1096-0341
Titre abrégé: Virology
Pays: United States
ID NLM: 0110674
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
08
06
2021
revised:
27
08
2021
accepted:
31
08
2021
pubmed:
12
9
2021
medline:
5
10
2021
entrez:
11
9
2021
Statut:
ppublish
Résumé
The COVID-19 pandemic has paralyzed the global economy and resulted in millions of deaths globally. People with co-morbidities like obesity, diabetes and hypertension are at an increased risk for severe COVID-19 illness. This is of overwhelming concern because 42% of Americans are obese, 30% are pre-diabetic and 9.4% have clinical diabetes. Here, we investigated the effect of obesity on disease severity following SARS-CoV-2 infection using a well-established mouse model of diet-induced obesity. Diet-induced obese and lean control C57BL/6 N mice, transduced for ACE2 expression using replication-defective adenovirus, were infected with SARS-CoV-2, and monitored for lung pathology, viral titers, and cytokine expression. No significant differences in tissue pathology or viral replication was observed between AdV transduced lean and obese groups, infected with SARS-CoV-2, but certain cytokines were expressed more significantly in infected obese mice compared to the lean ones. Notably, significant weight loss was observed in obese mice treated with the adenovirus vector, independent of SARS-CoV-2 infection, suggesting an obesity-dependent morbidity induced by the vector. These data indicate that the adenovirus-transduced mouse model of SARS-CoV-2 infection, as described here and elsewhere, may be inappropriate for nutrition studies.
Identifiants
pubmed: 34509029
pii: S0042-6822(21)00184-7
doi: 10.1016/j.virol.2021.08.014
pmc: PMC8414371
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
98-106Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL132236
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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