{"doi":"10.1093/toxsci/kfac049","title":"Low-Dose Cadmium Potentiates Metabolic Reprogramming Following Early-Life Respiratory Syncytial Virus Infection","abstract":"Respiratory syncytial virus (RSV) infection causes serious pulmonary disease and death in high-risk infants and elderly. Cadmium (Cd) is a toxic environmental metal contaminant and constantly exposed to humans. Limited information is available on Cd toxicity after early-life respiratory virus infection. In this study, we examined the effects of low-dose Cd exposure following early-life RSV infection on lung metabolism and inflammation using mouse and fibroblast culture models. C57BL/6J mice at 8 days old were exposed to RSV 2 times with a 4-week interval. A subset of RSV-infected mice was subsequently treated with Cd at a low dose in drinking water (RSV infection at infant age [RSVinf]+Cd) for 16 weeks. The results of inflammatory marker analysis showed that the levels of cytokines and chemokines were substantially higher in RSVinf+Cd group than other groups, implying that low-dose Cd following early-life RSV infection enhanced lung inflammation. Moreover, histopathology data showed that inflammatory cells and thickening of the alveolar walls as a profibrotic signature were evident in RSVinf+Cd. The metabolomics data revealed that RSVinf+Cd-caused metabolic disruption in histamine and histidine, vitamin D and urea cycle, and pyrimidine pathway accompanying with mechanistic target of rapamycin complex-1 activation. Taken together, our study demonstrates for the first time that cumulative Cd exposure following early-life RSV infection has a significant impact on subsequent inflammation and lung metabolism. Thus, early-life respiratory infection may reprogram metabolism and potentiate Cd toxicity, enhance inflammation, and cause fibrosis later in life.","journal":"Toxicological Sciences","year":2022,"id":261961,"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":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":300623,"name":"Matthew Ryan Smith","orcid":"0000-0002-8889-3477","position":1,"is_corresponding":false},{"id":435127,"name":"Ki‐Hye Kim","orcid":null,"position":2,"is_corresponding":false},{"id":434394,"name":"Youri Lee","orcid":"0000-0002-0905-5900","position":3,"is_corresponding":false},{"id":300624,"name":"Xin Hu","orcid":"0000-0003-2747-9085","position":4,"is_corresponding":false},{"id":713912,"name":"Xiaojia He","orcid":"0000-0001-8274-5564","position":5,"is_corresponding":false},{"id":302995,"name":"Michael Orr","orcid":null,"position":6,"is_corresponding":false},{"id":917208,"name":"Yan Chen","orcid":"0000-0002-7713-6913","position":7,"is_corresponding":false},{"id":301247,"name":"Sang‐Moo Kang","orcid":"0000-0001-6198-331X","position":8,"is_corresponding":false},{"id":231483,"name":"Dean P. Jones","orcid":"0000-0002-2090-0677","position":9,"is_corresponding":false},{"id":300625,"name":"Young‐Mi Go","orcid":"0000-0003-3353-0844","position":10,"is_corresponding":false},{"id":300622,"name":"Zachery Jarrell","orcid":"0000-0003-4670-1497","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T00:26:20.717229Z","pmid":"35512398","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":[]}