{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:05:25Z","timestamp":1759190725511,"version":"3.44.0"},"reference-count":43,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Roy G. Carver Trust"},{"name":"University of Iowa Carver College of Medicine and the Holden Cancer Center","award":["NIH P30 CA086862"],"award-info":[{"award-number":["NIH P30 CA086862"]}]},{"name":"Iowa Carver College of Medicine"},{"name":"Holden Cancer Center"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Viruses"],"abstract":"<jats:p>Adipocytes can be infected by SARS-CoV-2, potentially contributing to the obesity-associated severity of COVID-19. Circumstantial evidence points to angiotensin-converting enzyme 2 (ACE2) as the necessary receptor for adipocyte infection, but this has not been demonstrated experimentally. Using differentiated immortalized human preadipocyte lines that we developed, we found that visceral adipocytes express higher levels of ACE2 and are more susceptible to SARS-CoV-2 spike (S)-mediated luciferase-VSV infection than subcutaneous adipocytes. Overexpression of ACE2 significantly increased infection, whereas knockout of ACE2 significantly decreased S-mediated infection. Visceral adipocytes at baseline were susceptible to infection by SARS-CoV-2 (Delta variant); however, increased levels of viral transcript with time were not apparent. ACE2 knockout significantly decreased the susceptibility of visceral adipocytes to SARS-CoV-2, whereas overexpression of ACE2 resulted in increased SARS-CoV-2 infection and was associated with increased viral transcript levels with time, as well as induction of IL6, a marker of the proinflammatory response. Our results demonstrate that ACE2 confers susceptibility to SARS-CoV-2 infection of visceral adipocytes. Higher levels of ACE2 in these cells may play a role in establishment of infection and a proinflammatory response, potentially leading to pathogenesis.<\/jats:p>","DOI":"10.3390\/v17101311","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:00:32Z","timestamp":1759132832000},"page":"1311","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ACE2-Mediated Infection of Immortalized Human Visceral Adipocytes by SARS-CoV-2"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3885-2603","authenticated-orcid":false,"given":"Francoise A.","family":"Gourronc","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan I.","family":"Ahmann","sequence":"additional","affiliation":[{"name":"State Hygienic Laboratory, University of Iowa, Iowa City, IA 52241, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4985-2138","authenticated-orcid":false,"given":"Michael R.","family":"Rebagliati","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Scientific Editing and Research Communication Core, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4258-5046","authenticated-orcid":false,"given":"Aloysius J.","family":"Klingelhutz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4981","DOI":"10.1007\/s12325-020-01510-y","article-title":"Baseline Demographics and Clinical Characteristics Among 3471 US Patients Hospitalized with COVID-19 and Pulmonary Involvement: A Retrospective Study","volume":"37","author":"Best","year":"2020","journal-title":"Adv. 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