{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T02:38:21Z","timestamp":1781059101651,"version":"3.54.1"},"reference-count":70,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["R01 AI087683-01A1"],"award-info":[{"award-number":["R01 AI087683-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["AP19VSNL00C037"],"award-info":[{"award-number":["AP19VSNL00C037"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"LSU School of Veterinary Medicine Startup Fund awarded","award":["R01 AI087683-01A1"],"award-info":[{"award-number":["R01 AI087683-01A1"]}]},{"name":"LSU School of Veterinary Medicine Startup Fund awarded","award":["AP19VSNL00C037"],"award-info":[{"award-number":["AP19VSNL00C037"]}]},{"name":"LSU Economic Development Assistantship awarded","award":["R01 AI087683-01A1"],"award-info":[{"award-number":["R01 AI087683-01A1"]}]},{"name":"LSU Economic Development Assistantship awarded","award":["AP19VSNL00C037"],"award-info":[{"award-number":["AP19VSNL00C037"]}]},{"name":"NSTP Fellowship","award":["R01 AI087683-01A1"],"award-info":[{"award-number":["R01 AI087683-01A1"]}]},{"name":"NSTP Fellowship","award":["AP19VSNL00C037"],"award-info":[{"award-number":["AP19VSNL00C037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human cytomegalovirus (HCMV) is a ubiquitous pathogen that infects the majority of the world population and causes lifelong latent infection. HCMV has been shown to exacerbate cardiovascular diseases, including myocarditis, vascular sclerosis, and transplant vasculopathy. Recently, we have shown that murine CMV (MCMV) recapitulates the cardiovascular dysfunction observed in patients with HCMV-induced myocarditis. To understand the viral mechanisms involved in CMV-induced heart dysfunction, we further characterized cardiac function in response to MCMV and examined virally encoded G-protein-coupled receptor homologs (vGPCRs) US28 and M33 as potential factors that promote infection in the heart. We hypothesized that the CMV-encoded vGPCRs could exacerbate cardiovascular damage and dysfunction. Three viruses were used to evaluate the role of vGPCRs in cardiac dysfunction: wild-type MCMV, a M33-deficient virus (\u2206M33), and a virus with the M33 open reading frame (ORF) replaced with US28, an HCMV vGPCR (i.e., US28+). Our in vivo studies revealed that M33 plays a role in promoting cardiac dysfunction by increasing viral load and heart rate during acute infection. During latency, \u0394M33-infected mice demonstrated reduced calcification, altered cellular gene expression, and less cardiac hypertrophy compared with wild-type MCMV-infected mice. Ex vivo viral reactivation from hearts was less efficient in \u0394M33-infected animals. HCMV protein US28 expression restored the ability of the M33-deficient virus to reactivate from the heart. US28+ MCMV infection caused damage to the heart comparable with wild-type MCMV infection, suggesting that the US28 protein is sufficient to complement the function of M33 in the heart. Altogether, these data suggest a role for vGPCRs in viral pathogenesis in the heart and thus suggest that vGPCRs promote long-term cardiac damage and dysfunction.<\/jats:p>","DOI":"10.3390\/v15030711","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T03:02:08Z","timestamp":1678417328000},"page":"711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Viral G-Protein-Coupled Receptor Homologs M33 and US28 Promote Cardiac Dysfunction during Murine Cytomegalovirus Infection"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4026-7677","authenticated-orcid":false,"given":"Cassandra M.","family":"Bonavita","sequence":"first","affiliation":[{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1481-3013","authenticated-orcid":false,"given":"Timothy M.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Francis","sequence":"additional","affiliation":[{"name":"Department of Comparative Biological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7214-2767","authenticated-orcid":false,"given":"Helen E.","family":"Farrell","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Bioscience, University of Queensland, Brisbane 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Davis-Poynter","sequence":"additional","affiliation":[{"name":"Child Health Research Centre, University of Queensland, Brisbane 4101, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda D.","family":"Cardin","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1365-2796.2006.01618.x","article-title":"Does cytomegalovirus play a causative role in the development of various inflammatory diseases and cancer?","volume":"259","year":"2006","journal-title":"J. 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