{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T03:25:42Z","timestamp":1772249142641,"version":"3.50.1"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Previous studies suggested that the SARS-CoV-2 virus may gain access to the brain by using a route along the olfactory nerve. However, there is a general consensus that the obligatory virus entry receptor, angiotensin converting enzyme 2 (ACE2), is not expressed in olfactory receptor neurons, and the timing of arrival of the virus in brain targets is inconsistent with a neuronal transfer along olfactory projections. We determined whether nervus terminalis neurons and their peripheral and central projections should be considered as a potential alternative route from the nose to the brain. Nervus terminalis neurons in postnatal mice were double-labeled with antibodies against ACE2 and two nervus terminalis markers, gonadotropin-releasing hormone (GnRH) and choline acetyltransferase (CHAT). We show that a small fraction of CHAT-labeled nervus terminalis neurons, and the large majority of GnRH-labeled nervus terminalis neurons with cell bodies in the region between the olfactory epithelium and the olfactory bulb express ACE2 and cathepsins B and L. Nervus terminalis neurons therefore may provide a direct route for the virus from the nasal epithelium, possibly via innervation of Bowman\u2019s glands, to brain targets, including the telencephalon and diencephalon. This possibility needs to be examined in suitable animal models and in human tissues.<\/jats:p>","DOI":"10.3389\/fncel.2021.674123","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T02:18:35Z","timestamp":1625451515000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Expression of the ACE2 Virus Entry Protein in the Nervus Terminalis Reveals the Potential for an Alternative Route to Brain Infection in COVID-19"],"prefix":"10.3389","volume":"15","author":[{"given":"Katarzyna","family":"Bilinska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher S.","family":"von Bartheld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafal","family":"Butowt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1006\/viro.1993.1248","article-title":"The olfactory nerve and not the trigeminal nerve is the major site of CNS entry for mouse hepatitis virus, strain JHM.","volume":"194","author":"Barnett","year":"1993","journal-title":"Virology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2972","DOI":"10.1523\/JNEUROSCI.15-04-02972.1995","article-title":"Anterograde tracing of trigeminal afferent pathways from the murine tooth pulp to cortex using herpes simplex virus type 1.","volume":"15","author":"Barnett","year":"1995","journal-title":"J. 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