Direct activation of airway sensory C‐fibers by SARS‐CoV‐2 S1 spike protein
Abstract Respiratory viral infection can lead to activation of sensory afferent nerves as indicated by the consequential sore throat, sneezing, coughing, and reflex secretions. In addition to causing troubling symptoms, sensory nerve activation likely accelerates viral spreading. The mechanism how v...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.15900 |
| _version_ | 1827397863669235712 |
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| author | Joyce S. Kim Fei Ru Sonya Meeker Bradley J. Undem |
| author_facet | Joyce S. Kim Fei Ru Sonya Meeker Bradley J. Undem |
| author_sort | Joyce S. Kim |
| collection | DOAJ |
| description | Abstract Respiratory viral infection can lead to activation of sensory afferent nerves as indicated by the consequential sore throat, sneezing, coughing, and reflex secretions. In addition to causing troubling symptoms, sensory nerve activation likely accelerates viral spreading. The mechanism how viruses activate sensory nerve terminals during infection is unknown. In this study, we investigate whether coronavirus spike protein activates sensory nerves terminating in the airways. We used isolated vagally‐innervated mouse trachea‐lung preparation for two‐photon microscopy and extracellular electrophysiological recordings. Using two‐photon Ca2+ imaging, we evaluated a total number of 786 vagal bronchopulmonary nerves in six experiments. Approximately 49% of the sensory fibers were activated by S1 protein (4 μg/mL intratracheally). Extracellular nerve recording showed the S1 protein evoked action potential discharge in sensory C‐fibers; of 39 airway C‐fibers (one fiber per mouse), 17 were activated. Additionally, Fura‐2 Ca2+ imaging was performed on neurons dissociated from vagal sensory ganglia (n = 254 from 22 mice). The result showed that 63% of neurons responded to S1 protein. SARS‐CoV‐2 S1 protein can lead to direct activation of sensory C‐fiber nerve terminals in the bronchopulmonary tract. Direct activation of C‐fibers may contribute to coronavirus symptoms, and amplify viral spreading in a population. |
| first_indexed | 2024-03-08T19:18:03Z |
| format | Article |
| id | doaj.art-e8faeabc8ff140a180c8c734dfc64fea |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-03-08T19:18:03Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-e8faeabc8ff140a180c8c734dfc64fea2023-12-27T03:58:32ZengWileyPhysiological Reports2051-817X2023-12-011124n/an/a10.14814/phy2.15900Direct activation of airway sensory C‐fibers by SARS‐CoV‐2 S1 spike proteinJoyce S. Kim0Fei Ru1Sonya Meeker2Bradley J. Undem3Department of Medicine Johns Hopkins University School of Medicine Baltimore Maryland USADepartment of Medicine Johns Hopkins University School of Medicine Baltimore Maryland USADepartment of Medicine Johns Hopkins University School of Medicine Baltimore Maryland USADepartment of Medicine Johns Hopkins University School of Medicine Baltimore Maryland USAAbstract Respiratory viral infection can lead to activation of sensory afferent nerves as indicated by the consequential sore throat, sneezing, coughing, and reflex secretions. In addition to causing troubling symptoms, sensory nerve activation likely accelerates viral spreading. The mechanism how viruses activate sensory nerve terminals during infection is unknown. In this study, we investigate whether coronavirus spike protein activates sensory nerves terminating in the airways. We used isolated vagally‐innervated mouse trachea‐lung preparation for two‐photon microscopy and extracellular electrophysiological recordings. Using two‐photon Ca2+ imaging, we evaluated a total number of 786 vagal bronchopulmonary nerves in six experiments. Approximately 49% of the sensory fibers were activated by S1 protein (4 μg/mL intratracheally). Extracellular nerve recording showed the S1 protein evoked action potential discharge in sensory C‐fibers; of 39 airway C‐fibers (one fiber per mouse), 17 were activated. Additionally, Fura‐2 Ca2+ imaging was performed on neurons dissociated from vagal sensory ganglia (n = 254 from 22 mice). The result showed that 63% of neurons responded to S1 protein. SARS‐CoV‐2 S1 protein can lead to direct activation of sensory C‐fiber nerve terminals in the bronchopulmonary tract. Direct activation of C‐fibers may contribute to coronavirus symptoms, and amplify viral spreading in a population.https://doi.org/10.14814/phy2.15900C‐fibercoughsensory nervevagusvirus infection |
| spellingShingle | Joyce S. Kim Fei Ru Sonya Meeker Bradley J. Undem Direct activation of airway sensory C‐fibers by SARS‐CoV‐2 S1 spike protein Physiological Reports C‐fiber cough sensory nerve vagus virus infection |
| title | Direct activation of airway sensory C‐fibers by SARS‐CoV‐2 S1 spike protein |
| title_full | Direct activation of airway sensory C‐fibers by SARS‐CoV‐2 S1 spike protein |
| title_fullStr | Direct activation of airway sensory C‐fibers by SARS‐CoV‐2 S1 spike protein |
| title_full_unstemmed | Direct activation of airway sensory C‐fibers by SARS‐CoV‐2 S1 spike protein |
| title_short | Direct activation of airway sensory C‐fibers by SARS‐CoV‐2 S1 spike protein |
| title_sort | direct activation of airway sensory c fibers by sars cov 2 s1 spike protein |
| topic | C‐fiber cough sensory nerve vagus virus infection |
| url | https://doi.org/10.14814/phy2.15900 |
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