{"doi":"10.3390/v16040611","title":"Natural Killer Cells Do Not Attenuate a Mouse-Adapted SARS-CoV-2-Induced Disease in Rag2−/− Mice","abstract":"This study investigates the roles of T, B, and Natural Killer (NK) cells in the pathogenesis of severe COVID-19, utilizing mouse-adapted SARS-CoV-2-MA30 (MA30). To evaluate this MA30 mouse model, we characterized MA30-infected C57BL/6 mice (B6) and compared them with SARS-CoV-2-WA1 (an original SARS-CoV-2 strain) infected K18-human ACE2 (K18-hACE2) mice. We found that the infected B6 mice developed severe peribronchial inflammation and rapid severe pulmonary edema, but less lung interstitial inflammation than the infected K18-hACE2 mice. These pathological findings recapitulate some pathological changes seen in severe COVID-19 patients. Using this MA30-infected mouse model, we further demonstrate that T and/or B cells are essential in mounting an effective immune response against SARS-CoV-2. This was evident as Rag2−/− showed heightened vulnerability to infection and inhibited viral clearance. Conversely, the depletion of NK cells did not significantly alter the disease course in Rag2−/− mice, underscoring the minimal role of NK cells in the acute phase of MA30-induced disease. Together, our results indicate that T and/or B cells, but not NK cells, mitigate MA30-induced disease in mice and the infected mouse model can be used for dissecting the pathogenesis and immunology of severe COVID-19.","journal":"Viruses","year":2024,"id":442263,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9636,"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":1072633,"name":"Chenxiao Wang","orcid":"0000-0001-7950-9288","position":1,"is_corresponding":false},{"id":1255713,"name":"Alexis Katz","orcid":"0000-0002-3302-0759","position":2,"is_corresponding":false},{"id":545582,"name":"Zhen Chen","orcid":"0000-0002-4502-0801","position":3,"is_corresponding":false},{"id":372010,"name":"Mohammad Islamuddin","orcid":"0000-0002-4929-8931","position":4,"is_corresponding":false},{"id":633100,"name":"Haoran Yang","orcid":"0000-0002-6464-8450","position":5,"is_corresponding":false},{"id":683404,"name":"Sarah E. Scheuermann","orcid":"0000-0002-9899-997X","position":6,"is_corresponding":false},{"id":445435,"name":"Kelly Goff","orcid":"0000-0003-2682-6532","position":7,"is_corresponding":false},{"id":259617,"name":"Nicholas J. Maness","orcid":"0000-0002-9332-7891","position":8,"is_corresponding":false},{"id":259605,"name":"Robert V. Blair","orcid":"0000-0001-9616-9414","position":9,"is_corresponding":false},{"id":246970,"name":"Jay K. Kolls","orcid":"0000-0001-5151-6304","position":10,"is_corresponding":false},{"id":237300,"name":"Xuebin Qin","orcid":"0000-0001-9875-983X","position":11,"is_corresponding":false},{"id":704987,"name":"Calder Ellsworth","orcid":"0000-0001-7111-525X","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:01:15.932178Z","pmid":"38675952","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":[]}