{"doi":"10.1002/jmv.70102","title":"Human Primary Macrophages Can Transmit Coxsackie B4 Virus to Pancreatic Cells In Vitro","abstract":"Type 1 diabetes (T1D) is a chronic autoimmune condition that occurs when the body's immune cells destroy the insulin-producing cells (beta-cells) in the pancreas, which leads to elevated blood sugar (glucose) level or hyperglycemic condition. It is the most common form of diabetes in children, which is believed to affect more than 500, 000 children worldwide [1]. T1D is most common in Scandinavian and other European countries or countries with high European ancestry but is relatively rare in East Asian countries [1]. Diagnosis rates of T1D peak at ages 10–14 [1], though the presence of T1D-associated autoantibodies may result in T1D being mistaken for type 2 diabetes (T2D) in older adults or in an exacerbation of T2D development [2-5]. Disease development is divided into three stages, with stage 1 being characterized by the initiation of beta-cell loss, stage 2 with changes in sugar level regulation, and stage 3 with symptom onset when the disease is typically diagnosed. Treatment requires the use of administered insulin to regulate blood sugar level, but T1D condition increases the risk for long-term complications such as diabetic retinopathy, neuropathy and cardiovascular disease. As aforementioned, most cases of T1D result from an auto-immune mediated destruction of pancreatic beta-cells that produce insulin. While the triggers for initiating this beta-cell destruction have yet to be fully understood, ample clinical and preclinical studies have associated viral infection with T1D development in genetically susceptible individuals. Several mechanisms have been proposed to explain the phenomenon of virus-induced destruction of beta-cells, such as virus-mediated interference with auto-immunity checkpoints or molecular mimicry, in which viral infection may stimulate the production of antibodies against a viral protein that may inadvertently trigger an autoimmune response against antigenically similar protein or protein components of the beta cells, which can lead to pancreatic tissue pathogenesis resulting from either the acute or chronic viral infection and tissue inflammation [6, 7]. Among suspected viral culprits, enteroviruses (and most prominently coxsackie B viruses) have the strongest correlational clinical data linking viral infection [8-12], detection of viral genomic contents [13-17] and seropositivity [9, 16] with T1D development [18-20]. Furthermore, animal and cell culture experiments have demonstrated cell death [11, 12] and the onset of auto-immune diabetes [21] to enteroviral infection. However, it is important to note that other studies have not found significant associations between T1D and enteroviral infection under certain circumstances [7, 22, 23] or that T1D development is likely to be co-dependent on additional genetic and environmental factors [24] given the high rate of enteroviral infection among the general population [25, 26]. In cases where enteroviral infection is suspected to be a culprit in T1D development, circulating monocytes and tissue-resident macrophages are thought to carry the virus to pancreas [27] (Figure 1). Furthermore, infiltrating macrophages have been repeatedly found in pancreatic tissues of T1D patients [28] and are necessary for the disease development in enterovirus-infected mice [29, 30], implicating the potential role of macrophages in transmitting the virus to pancreatic cells and in inflammatory tissue destruction. To investigate the potential interactions between enterovirus-infected macrophages and pancreatic cells, a recently accepted article by Vergez and colleagues utilized an in-vitro cell-culture system consisting of primary human-derived macrophages and a human pancreatic cell line to track enteroviral infection and transmission as well as macrophage activation and pancreatic cell lysis [31]. To do this, the authors infected human's monocyte-derived macrophages [via stimulation of primary monocytes of healthy donors with the macrophage-colony stimulating factor (M-","journal":"Journal of Medical Virology","year":2024,"id":482458,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"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":233282,"name":"Hinh Ly","orcid":"0000-0001-8271-2033","position":1,"is_corresponding":false},{"id":233278,"name":"Morgan Brisse","orcid":"0000-0002-7040-4495","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T02:07:18.280369Z","pmid":"39614711","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":[]}