{"doi":"10.1101/2020.11.20.392357","title":"Antibody-dependent enhancement representing\n                  <i>in vitro</i>\n                  infective progeny virus titer correlates with the viremia level in dengue patients","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>\n                  Dengue virus (DENV) distributes throughout tropical and subtropical countries and causes dengue fever (DF) and dengue hemorrhagic fever in humans. Some DF patients suddenly develop severe symptoms after the defervescent period. Although the pathogenic mechanism of the severe symptoms has not been fully elucidated, the viremia level in the early phase has been shown to correlate with the disease severity. One of the hypotheses is that a phenomenon called antibody-dependent enhancement (ADE) of infection leads to a high level of viremia. To examine the plausibility of this hypothesis, we examined the relationship between\n                  <jats:italic>in vitro</jats:italic>\n                  ADE activity and\n                  <jats:italic>in vivo</jats:italic>\n                  viral load quantity in six patients with dengue diseases. An autologous DENV strain was isolated from each of the six patients. Blood samples were then collected at multiple time points between the acute and defervescent phases, and the balance between neutralizing and enhancing activities against the autologous and prototype viruses was examined. As the antibody levels against DENV were rapidly increased, ADE activity was decreased over time or partially maintained against some viruses at low serum dilution. In addition, positive correlations were observed between ADE activity representing\n                  <jats:italic>in vitro</jats:italic>\n                  progeny virus production and viremia levels in patient plasma samples. Therefore, the measurement of ADE activity in dengue-seropositive samples may help to predict the impact of viral load in the subsequent DENV infection.\n                </jats:p>\n                <jats:sec>\n                  <jats:title>IMPORTANCE</jats:title>\n                  <jats:p>\n                    It has not been fully elucidated how the phenomenon of antibody-dependent enhancement (ADE) affects the pathogenesis of severe dengue diseases, although high viremia levels have been epidemiologically demonstrated to be associated with the disease severity. Here, we show that ADE in the acute-phase patient sera exhibited significantly different activities against autologous and lab strains than ADE in the defervescent-phase sera. Further, the enhancement of progeny virus production activity, which is one of the factors to evaluate ADE\n                    <jats:italic>in vitro</jats:italic>\n                    , was significantly correlated with the levels of viral load in the patient blood circulation. This suggests that measurement of the\n                    <jats:italic>in vitro</jats:italic>\n                    enhancing progeny virus titers might be used to predict the impact of\n                    <jats:italic>in vivo</jats:italic>\n                    DENV viremia level. Our present findings could contribute to a method to forecast disease severity for seropositive populations who would be at risk of developing severe disease in the event of heterotypic DENV infection.\n                  </jats:p>\n                </jats:sec>","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":null,"id":25831,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":136078,"name":"Hisham Ahmed Imad","orcid":null,"position":1,"is_corresponding":false},{"id":136079,"name":"Weerapong Phumratanaprapin","orcid":null,"position":2,"is_corresponding":false},{"id":136080,"name":"Juthamas Phadungsombat","orcid":null,"position":3,"is_corresponding":false},{"id":136081,"name":"Eiji Konishi","orcid":null,"position":4,"is_corresponding":false},{"id":136082,"name":"Tatsuo Shioda","orcid":null,"position":5,"is_corresponding":false},{"id":136077,"name":"Atsushi Yamanaka","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34117329","pmcid":null,"openalex_id":"https://openalex.org/W3110019753","authors":[],"funders":[{"funder_name":"Fundação para a Ciência e a Tecnologia, I.P.","grant_id":"PTDC/CCI-BIO/29266/2017","title":"Deep Drug Discovery and Deployment"}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":2,"citation_trend":[],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/11/23/2020.11.20.392357.full.pdf","host_type":"repository"},{"url":"https://www.nature.com/articles/s41598-021-91793-0.pdf","host_type":"GREEN"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/11/23/2020.11.20.392357.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2020.11.20.392357","host_type":"publisher"},{"url":"https://doi.org/10.1101/2020.11.20.392357","host_type":"repository"},{"url":"https://doi.org/10.1038/s41598-021-91793-0","host_type":""},{"url":"https://dx.doi.org/10.60692/9sxph-ak507","host_type":""},{"url":"https://dx.doi.org/10.60692/ergfm-95j08","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/34117329","host_type":""},{"url":"http://dx.doi.org/10.1038/s41598-021-91793-0","host_type":""},{"url":"https://doaj.org/article/fe6708c7f6214a3189d92335ffda592b","host_type":""},{"url":"https://dx.doi.org/10.1038/s41598-021-91793-0","host_type":""},{"url":"https://dx.doi.org/10.1101/2020.11.20.392357","host_type":""}],"fields_of_study":["Mosquito-borne diseases and control","Viral Infections and Vectors","Vector-borne infectious diseases","Medicine","Biology","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":[],"keywords":["Viremia","Dengue fever","Dengue virus","Virology","Antibody","Antibody-dependent enhancement","Titer","Virus","Viral load","Immunology","Biology","Neutralizing antibody","Pathogenesis","Antibody titer","Medicine","Science","FOS: Health sciences","Dengue vaccine","Antibodies, Viral","Article","Dengue","Chlorocebus aethiops","Health Sciences","In vivo","Animals","Humans","Global Impact of Arboviral Diseases","Vero Cells","Immunology and Microbiology","FOS: Clinical medicine","Q","R","Public Health, Environmental and Occupational Health","Life Sciences","Infectious Diseases","Viral disease","Tick-Borne Diseases and Pathogens Transmission","Parasitology","K562 Cells","Viral Hemorrhagic Fevers and Zoonotic Infections","Biotechnology"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T08:34:50.325212Z","pmid":null,"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":[]}