{"doi":"10.21873/invivo.13605","title":"SARS-CoV-2 Spike Protein Induces Oxidative Stress and Senescence in Mouse and Human Lung","abstract":"BACKGROUND/AIM: There is concern that people who had COVID-19 will develop pulmonary fibrosis. Using mouse models, we compared pulmonary inflammation following injection of the spike protein of SARS-CoV-2 (COVID-19) to radiation-induced inflammation to demonstrate similarities between the two models. SARS-CoV-2 (COVID-19) induces inflammatory cytokines and stress responses, which are also common to ionizing irradiation-induced acute pulmonary damage. Cellular senescence, which is a late effect following exposure to SARS-CoV-2 as well as radiation, was investigated. MATERIALS AND METHODS: We evaluated the effect of SARS-CoV-2 spike protein compared to ionizing irradiation in K18-hACE2 mouse lung, human lung cell lines, and in freshly explanted human lung. We measured reactive oxygen species, DNA double-strand breaks, stimulation of transforming growth factor-beta pathways, and cellular senescence following exposure to SARS-CoV-2 spike protein, irradiation or SARS-COV-2 and irradiation. We also measured the effects of the antioxidant radiation mitigator MMS350 following irradiation or exposure to SARS-CoV-2. RESULTS: SARS-CoV-2 spike protein induced reactive oxygen species, DNA double-strand breaks, transforming growth factor-β signaling pathways, and senescence, which were exacerbated by prior or subsequent ionizing irradiation. The water-soluble radiation countermeasure, MMS350, reduced spike protein-induced changes. CONCLUSION: In both the SARS-Co-2 and the irradiation mouse models, similar responses were seen indicating that irradiation or exposure to SARS-CoV-2 virus may lead to similar lung diseases such as pulmonary fibrosis. Combination of irradiation and SARS-CoV-2 may result in a more severe case of pulmonary fibrosis. Cellular senescence may explain some of the late effects of exposure to SARS-CoV-2 spike protein and to ionizing irradiation.","journal":"In Vivo","year":2024,"id":434156,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9642,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":674375,"name":"Wen‐Chi Hou","orcid":"0000-0002-9565-7018","position":1,"is_corresponding":false},{"id":674856,"name":"Donna Shields","orcid":null,"position":2,"is_corresponding":false},{"id":674855,"name":"Renee Fisher","orcid":null,"position":3,"is_corresponding":false},{"id":228850,"name":"Michael W. Epperly","orcid":"0000-0002-6214-6887","position":4,"is_corresponding":false},{"id":1262,"name":"Inderpal Sarkaria","orcid":null,"position":5,"is_corresponding":false},{"id":247975,"name":"Peter Wipf","orcid":"0000-0001-7693-5863","position":6,"is_corresponding":false},{"id":105025,"name":"Hong Wang","orcid":"0000-0003-0477-2908","position":7,"is_corresponding":false},{"id":110066,"name":"Joel S. Greenberger","orcid":"0000-0003-2271-7566","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:59:53.957667Z","pmid":"38936937","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}