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

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dc.contributor.authorRai, Pallavien
dc.contributor.authorChuong, Christinaen
dc.contributor.authorLeRoith, Tanyaen
dc.contributor.authorSmyth, James W.en
dc.contributor.authorPanov, Juliaen
dc.contributor.authorLevi, Mosheen
dc.contributor.authorKehn-Hall, Kyleneen
dc.contributor.authorDuggal, Nisha K.en
dc.contributor.authorWeger-Lucarelli, Jamesen
dc.date.accessioned2021-11-22T17:41:00Zen
dc.date.available2021-11-22T17:41:00Zen
dc.date.issued2021-11-01en
dc.date.updated2021-11-22T17:40:52Zen
dc.description.abstractThe 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.en
dc.description.versionPublished versionen
dc.format.extentPages 98-106en
dc.format.extent9 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.virol.2021.08.014en
dc.identifier.eissn1089-862Xen
dc.identifier.issn0042-6822en
dc.identifier.orcidDuggal, Nisha [0000-0002-9893-8069]en
dc.identifier.orcidKehn-Hall, Kylene [0000-0001-8036-7213]en
dc.identifier.orcidLeRoith, Tanya [0000-0002-1196-6949]en
dc.identifier.otherS0042-6822(21)00184-7 (PII)en
dc.identifier.pmid34509029en
dc.identifier.urihttp://hdl.handle.net/10919/106707en
dc.identifier.volume563en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000700278300004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectLife Sciences & Biomedicineen
dc.subjectVirologyen
dc.subjectCOVID-19en
dc.subjectDiet-induced obesityen
dc.subjecthACE2en
dc.subjectReplication-defective adenovirusen
dc.subjectTissueen
dc.subjectPathologyen
dc.subjectACUTE RESPIRATORY SYNDROMEen
dc.subjectSYNDROME CORONAVIRUS INFECTIONen
dc.subjectIMMUNE-RESPONSESen
dc.subjectMORTALITYen
dc.subjectSARSen
dc.subjectVirologyen
dc.subject06 Biological Sciencesen
dc.subject07 Agricultural and Veterinary Sciencesen
dc.subject11 Medical and Health Sciencesen
dc.subject.meshVero Cellsen
dc.subject.meshAnimalsen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshObesityen
dc.subject.meshDisease Models, Animalen
dc.subject.meshMorbidityen
dc.subject.meshComorbidityen
dc.subject.meshFemaleen
dc.subject.meshMaleen
dc.subject.meshHEK293 Cellsen
dc.subject.meshChlorocebus aethiopsen
dc.subject.meshCOVID-19en
dc.titleAdenovirus transduction to express human ACE2 causes obesity-specific morbidity in mice, impeding studies on the effect of host nutritional status on SARS-CoV-2 pathogenesisen
dc.title.serialVirologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2021-08-31en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Durelle Scotten

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