{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:16:37Z","timestamp":1760058997254,"version":"build-2065373602"},"reference-count":74,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fralin Life Sciences Institute at Virginia Tech"},{"name":"Virginia Tech Subvention Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Neurological symptoms involving the central nervous system (CNS) and peripheral nervous system (PNS) are common complications of acute COVID-19 as well as post-COVID conditions. Most research into these neurological sequalae focuses on the CNS, disregarding the PNS. Guinea pigs were previously shown to be useful models of disease during the SARS-CoV-1 epidemic. However, their suitability for studying SARS-CoV-2 has not been experimentally demonstrated. To assess the suitability of guinea pigs as models for SARS-CoV-2 infection and the impact of SARS-CoV-2 infection on the PNS, and to determine routes of CNS invasion through the PNS, we intranasally infected wild-type Dunkin-Hartley guinea pigs with ancestral SARS-CoV-2 USA-WA1\/2020. We assessed PNS sensory neurons (trigeminal ganglia, dorsal root ganglia), autonomic neurons (superior cervical ganglia), brain regions (olfactory bulb, brainstem, cerebellum, cortex, hippocampus), lungs, and blood for viral RNA (RT-qPCR), protein (immunostaining), and infectious virus (plaque assay) at three- and six-days post infection. We show that guinea pigs, which have previously been used as a model of SARS-CoV-1 pulmonary disease, are not susceptible to intranasal infection with ancestral SARS-CoV-2, and are not useful models in assessing neurological impacts of infection with SARS-CoV-2 isolates from the early pandemic.<\/jats:p>","DOI":"10.3390\/v17050706","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T06:10:44Z","timestamp":1747289444000},"page":"706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Guinea Pigs Are Not a Suitable Model to Study Neurological Impacts of Ancestral SARS-CoV-2 Intranasal Infection"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2243-3793","authenticated-orcid":false,"given":"Jonathan D.","family":"Joyce","sequence":"first","affiliation":[{"name":"Translational Biology, Medicine and Health, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA"},{"name":"Center for Emerging Zoonotic and Arthropod-Borne Pathogens, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greyson A.","family":"Moore","sequence":"additional","affiliation":[{"name":"Biomedical and Veterinary Science, Virginia Maryland College of Veterinary Medicine, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3177-6042","authenticated-orcid":false,"given":"Christopher K.","family":"Thompson","sequence":"additional","affiliation":[{"name":"School of Neuroscience, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8941-8010","authenticated-orcid":false,"given":"Andrea S.","family":"Bertke","sequence":"additional","affiliation":[{"name":"Center for Emerging Zoonotic and Arthropod-Borne Pathogens, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA"},{"name":"Population Health Sciences, Virginia Maryland College of Veterinary Medicine, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"ref_1","first-page":"324","article-title":"The guinea pig as a model of infectious diseases","volume":"58","author":"McMurray","year":"2008","journal-title":"Comp. 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