{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:48:45Z","timestamp":1777610925830,"version":"3.51.4"},"posted":{"date-parts":[[2024,1,11]]},"group-title":"Neuroscience","reference-count":68,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,1,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  SARS-CoV-2, the virus responsible for COVID-19, triggers symptoms such as sneezing, aches and pain.\n                  <jats:sup>1<\/jats:sup>\n                  These symptoms are mediated by a subset of sensory neurons, known as nociceptors, that detect noxious stimuli, densely innervate the airway epithelium, and interact with airway resident epithelial and immune cells.\n                  <jats:sup>2\u20136<\/jats:sup>\n                  However, the mechanisms by which viral infection activates these neurons to trigger pain and airway reflexes are unknown. Here, we show that the coronavirus papain-like protease (PLpro) directly activates airway-innervating trigeminal and vagal nociceptors in mice and human iPSC-derived nociceptors. PLpro elicits sneezing and acute pain in mice and triggers the release of neuropeptide calcitonin gene-related peptide (CGRP) from airway afferents. We find that PLpro-induced sneeze and pain requires the host TRPA1 ion channel that has been previously demonstrated to mediate pain, cough, and airway inflammation.\n                  <jats:sup>7\u20139<\/jats:sup>\n                  Our findings are the first demonstration of a viral product that directly activates sensory neurons to trigger pain and airway reflexes and highlight a new role for PLpro and nociceptors in COVID-19.\n                <\/jats:p>","DOI":"10.1101\/2024.01.10.575114","type":"posted-content","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T18:15:11Z","timestamp":1704996911000},"source":"Crossref","is-referenced-by-count":4,"title":["SARS-CoV-2 papain-like protease activates nociceptors to drive sneeze and pain"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0737-813X","authenticated-orcid":false,"given":"Sonali S.","family":"Mali","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1167-6287","authenticated-orcid":false,"given":"Zhongyan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Cronce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uyen","family":"Vo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cliff","family":"Vuong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0600-1253","authenticated-orcid":false,"given":"Yalda","family":"Moayedi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5061-6618","authenticated-orcid":false,"given":"Jeffery S.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6809-8951","authenticated-orcid":false,"given":"Diana M.","family":"Bautista","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024011303350617000_2024.01.10.575114v1.1","doi-asserted-by":"crossref","unstructured":"Bliddal, S. et al. 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