{"doi":"10.1002/jmv.29579","title":"The use of human iPSC‐derived alveolar organoids to explore SARS‐CoV‐2 variant infections and host responses","abstract":"Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) primarily targets the respiratory system. Physiologically relevant human lung models are indispensable to investigate virus-induced host response and disease pathogenesis. In this study, we generated human induced pluripotent stem cell (iPSC)-derived alveolar organoids (AOs) using an established protocol that recapitulates the sequential steps of in vivo lung development. AOs express alveolar epithelial type II cell protein markers including pro-surfactant protein C and ATP binding cassette subfamily A member 3. Compared to primary human alveolar type II cells, AOs expressed higher mRNA levels of SARS-CoV-2 entry factors, angiotensin-converting enzyme 2 (ACE2), asialoglycoprotein receptor 1 (ASGR1) and basigin (CD147). Considering the localization of ACE2 on the apical side in AOs, we used three AO models, apical-in, sheared and apical-out for SARS-CoV-2 infection. All three models of AOs were robustly infected with the SARS-CoV-2 irrespective of ACE2 accessibility. Antibody blocking experiment revealed that ASGR1 was the main receptor for SARS-CoV2 entry from the basolateral in apical-in AOs. AOs supported the replication of SARS-CoV-2 variants WA1, Alpha, Beta, Delta, and Zeta and Omicron to a variable degree with WA1 being the highest and Omicron being the least. Transcriptomic profiling of infected AOs revealed the induction of inflammatory and interferon-related pathways with NF-κB signaling being the predominant host response. In summary, iPSC-derived AOs can serve as excellent human lung models to investigate infection of SARS-CoV-2 variants and host responses from both apical and basolateral sides.","journal":"Journal of Medical Virology","year":2024,"id":432893,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9306,"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":504504,"name":"Kishore Vaddadi","orcid":"0000-0003-0320-9064","position":1,"is_corresponding":false},{"id":493863,"name":"Pulavendran Sivasami","orcid":"0000-0002-9816-8527","position":2,"is_corresponding":false},{"id":392702,"name":"Chaoqun Huang","orcid":"0000-0001-8015-6467","position":3,"is_corresponding":false},{"id":480027,"name":"Yurong Liang","orcid":null,"position":4,"is_corresponding":false},{"id":394031,"name":"Samuel Pushparaj","orcid":null,"position":5,"is_corresponding":false},{"id":233693,"name":"Xufang Deng","orcid":"0000-0002-7604-3627","position":6,"is_corresponding":false},{"id":244495,"name":"Rudragouda Channappanavar","orcid":"0000-0002-7608-1922","position":7,"is_corresponding":false},{"id":331378,"name":"Jordan P. Metcalf","orcid":"0000-0003-4359-5270","position":8,"is_corresponding":false},{"id":392703,"name":"Lin Liu","orcid":"0000-0002-4811-4897","position":9,"is_corresponding":false},{"id":918328,"name":"Chaitanya Gandikota","orcid":"0000-0001-8876-4168","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T01:59:39.937122Z","pmid":"38572923","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":[]}