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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.
Rai, Pallavi; Chuong, Christina; LeRoith, Tanya; Smyth, James W; Panov, Julia; Levi, Moshe; Kehn-Hall, Kylene; Duggal, Nisha K; Lucarelli, James-Weger.
  • Rai P; Department of Biomedical Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA.
  • Chuong C; Department of Biomedical Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA.
  • LeRoith T; Department of Biomedical Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA.
  • Smyth JW; Center for Heart and Reparative Medicine, Fralin Biomedical Research Institute, Roanoke, VA, USA; Department of Biological Sciences, College of Science, Virginia Polytechnic State Institute and State University, Blacksburg, VA, USA; Department of Basic Science Education, Virginia Tech Carilion Schoo
  • Panov J; Tauber Bioinformatics Research Center, Haifa 3498838, Israel; Sagol Department of Neurobiology, University of Haifa, Haifa 3498838, Israel.
  • Levi M; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC, USA.
  • Kehn-Hall K; Department of Biomedical Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA.
  • Duggal NK; Department of Biomedical Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA.
  • Lucarelli JW; Department of Biomedical Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA. Electronic address: weger@vt.edu.
Virology ; 563: 98-106, 2021 11.
Article in English | MEDLINE | ID: covidwho-1386714
Preprint
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ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Disease Models, Animal / COVID-19 / Obesity Type of study: Etiology study / Randomized controlled trials Limits: Animals / Female / Humans / Male Language: English Journal: Virology Year: 2021 Document Type: Article Affiliation country: J.virol.2021.08.014

Full text: Available Collection: International databases Database: MEDLINE Main subject: Disease Models, Animal / COVID-19 / Obesity Type of study: Etiology study / Randomized controlled trials Limits: Animals / Female / Humans / Male Language: English Journal: Virology Year: 2021 Document Type: Article Affiliation country: J.virol.2021.08.014