{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:19:20Z","timestamp":1790727560355,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010255","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI146420"],"award-info":[{"award-number":["R01AI146420"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institutional start-up funds"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Nucleoside modified mRNA combined with Acuitas Therapeutics\u2019 lipid nanoparticles (LNPs) has been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs\u2019 ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper (Tfh) cells and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, these mice remained protected from lethal influenza and SARS-CoV-2 challenges. We further found that IL-6, unlike neutrophils, was required to generate normal Tfh cells and antibody responses, but not for protection from influenza challenge.<\/jats:p>\n                  <jats:p>In summary, here we bring evidence that the mRNA-LNP platform can support the induction of protective immune responses in the absence of certain innate immune cells and cytokines.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010255","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T13:39:59Z","timestamp":1643031599000},"page":"e1010255","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 immune responses"],"prefix":"10.1371","volume":"18","author":[{"given":"Sonia","family":"Ndeupen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Bouteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Herbst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonya","family":"Jacobsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas E.","family":"Powers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Hutchins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drishya","family":"Kurup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila Zabihi","family":"Diba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Ramage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9770-800X","authenticated-orcid":true,"given":"Botond Z.","family":"Igy\u00e1rt\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"ppat.1010255.ref001","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.immuni.2005.06.008","article-title":"Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA","volume":"23","author":"K Karik\u00f3","year":"2005","journal-title":"Immunity"},{"key":"ppat.1010255.ref002","doi-asserted-by":"crossref","first-page":"e142","DOI":"10.1093\/nar\/gkr695","article-title":"Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA","volume":"39","author":"K Karik\u00f3","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ppat.1010255.ref003","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nature21428","article-title":"Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination","volume":"543","author":"N Pardi","year":"2017","journal-title":"Nature"},{"key":"ppat.1010255.ref004","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1084\/jem.20171450","article-title":"Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses","volume":"215","author":"N Pardi","year":"2018","journal-title":"J Exp Med"},{"key":"ppat.1010255.ref005","author":"M-G Alameh","year":"2020","journal-title":"Messenger RNA-Based Vaccines Against Infectious Diseases"},{"key":"ppat.1010255.ref006","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1038\/mt.2008.200","article-title":"Incorporation of Pseudouridine Into mRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability","volume":"16","author":"K Karik\u00f3","year":"2008","journal-title":"Mol Ther"},{"key":"ppat.1010255.ref007","article-title":"The mRNA-LNP platform\u2019s lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory","author":"S Ndeupen","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010255.ref008","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev-immunol-020711-074950","article-title":"The Dendritic Cell Lineage: Ontogeny and Function of Dendritic Cells and Their Subsets in the Steady State and the Inflamed Setting","volume":"31","author":"M Merad","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"ppat.1010255.ref009","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.02169","article-title":"Determination of T Follicular Helper Cell Fate by Dendritic Cells","volume":"9","author":"JK Krishnaswamy","year":"2018","journal-title":"Front Immunol"},{"key":"ppat.1010255.ref010","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.immuni.2020.07.019","article-title":"A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice","volume":"53","author":"D Laczk\u00f3","year":"2020","journal-title":"Immunity"},{"key":"ppat.1010255.ref011","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1056\/NEJMoa2027906","article-title":"Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates","volume":"383","author":"EE Walsh","year":"2020","journal-title":"N Engl J Med"},{"key":"ppat.1010255.ref012","doi-asserted-by":"crossref","first-page":"eaam9169","DOI":"10.1126\/sciimmunol.aam9169","article-title":"Migratory CD11b+ conventional dendritic cells induce T follicular helper cell-dependent antibody responses","volume":"2","author":"JK Krishnaswamy","year":"2017","journal-title":"Sci Immunol"},{"key":"ppat.1010255.ref013","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.01134","article-title":"DC Subsets Regulate Humoral Immune Responses by Supporting the Differentiation of Distinct Tfh Cells","volume":"10","author":"A Bouteau","year":"2019","journal-title":"Front Immunol"},{"key":"ppat.1010255.ref014","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1016\/j.jid.2017.04.016","article-title":"Critical Role for Skin-Derived Migratory DCs and Langerhans Cells in TFH and GC Responses after Intradermal Immunization","volume":"137","author":"C Levin","year":"2017","journal-title":"J Invest Dermatol"},{"key":"ppat.1010255.ref015","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/j.jaci.2015.04.001","article-title":"Skin dendritic cells induce follicular helper T cells and protective humoral immune responses","volume":"136","author":"C Yao","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"ppat.1010255.ref016","doi-asserted-by":"crossref","first-page":"842","DOI":"10.4049\/jimmunol.1101176","article-title":"Targeting antigen to mouse dendritic cells via Clec9A induces potent CD4 T cell responses biased toward a follicular helper phenotype","volume":"187","author":"MH Lahoud","year":"2011","journal-title":"J Immunol"},{"key":"ppat.1010255.ref017","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.immuni.2005.10.008","article-title":"Epidermal langerhans cell-deficient mice develop enhanced contact hypersensitivity","volume":"23","author":"DH Kaplan","year":"2005","journal-title":"Immunity"},{"key":"ppat.1010255.ref018","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1084\/jem.20091627","article-title":"Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells","volume":"207","author":"BT Edelson","year":"2010","journal-title":"J Exp Med"},{"key":"ppat.1010255.ref019","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1084\/jem.20130728","article-title":"Intestinal lamina propria dendritic cells maintain T cell homeostasis but do not affect commensalism","volume":"210","author":"NE Welty","year":"2013","journal-title":"J Exp Med"},{"key":"ppat.1010255.ref020","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1038\/s41467-018-05482-0","article-title":"Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies","volume":"9","author":"N Pardi","year":"2018","journal-title":"Nat Commun"},{"key":"ppat.1010255.ref021","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1128\/JVI.02012-06","article-title":"Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus","volume":"81","author":"PB Mccray","year":"2007","journal-title":"J Virol"},{"key":"ppat.1010255.ref022","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.4049\/jimmunol.1203032","article-title":"Cutting edge: STAT1 is required for IL-6-mediated Bcl6 induction for early follicular helper cell differentiation","volume":"190","author":"YS Choi","year":"2013","journal-title":"J Immunol"},{"key":"ppat.1010255.ref023","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1182\/blood-2008-04-154682","article-title":"Interleukin-6\/STAT3 signaling regulates the ability of naive T cells to acquire B-cell help capacities","volume":"113","author":"F Eddahri","year":"2009","journal-title":"Blood"},{"key":"ppat.1010255.ref024","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/intimm\/dxq030","article-title":"IL-6: from its discovery to clinical applications","volume":"22","author":"T. Kishimoto","year":"2010","journal-title":"Int Immunol"},{"key":"ppat.1010255.ref025","article-title":"How Neutrophils Shape Adaptive Immune Responses","volume":"6","author":"PHC Leliefeld","year":"2015","journal-title":"Front Immunol"},{"key":"ppat.1010255.ref026","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.coph.2006.03.009","article-title":"Two way communication between neutrophils and dendritic cells","volume":"6","author":"IS Ludwig","year":"2006","journal-title":"Curr Opin Pharmacol"},{"key":"ppat.1010255.ref027","first-page":"1","article-title":"The regulatory roles of neutrophils in adaptive immunity","author":"Y Li","year":"2019","journal-title":"Cell Communication and Signaling. BioMed Central"},{"key":"ppat.1010255.ref028","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1189\/jlb.1012540","article-title":"Crosstalk between neutrophils and dendritic cells: a context-dependent process","volume":"94","author":"S Schuster","year":"2012","journal-title":"J Leukoc Biol"},{"key":"ppat.1010255.ref029","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1084\/jem.20041276","article-title":"Neutrophils mediate immune modulation of dendritic cells through glycosylation-dependent interactions between Mac-1 and DC-SIGN","volume":"201","author":"KPJM Van Gisbergen","year":"2005","journal-title":"J Exp Med"},{"key":"ppat.1010255.ref030","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1189\/jlb.0407247","article-title":"Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice","volume":"83","author":"JM Daley","year":"2008","journal-title":"J Leukoc Biol"},{"key":"ppat.1010255.ref031","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/nature11531","article-title":"Compensatory dendritic cell development mediated by BATF\u2013IRF interactions","volume":"490","author":"R Tussiwand","year":"2012","journal-title":"Nature"},{"key":"ppat.1010255.ref032","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.immuni.2011.08.008","article-title":"CD8\u03b1+ Dendritic Cells Are the Critical Source of Interleukin-12 that Controls Acute Infection by Toxoplasma gondii Tachyzoites","volume":"35","author":"M Mashayekhi","year":"2011","journal-title":"Immunity"},{"key":"ppat.1010255.ref033","first-page":"1","article-title":"Antibody-Dependent Cellular Cytotoxicity (ADCC)","author":"VR G\u00f3mez Rom\u00e1n","year":"2014","journal-title":"Antibody Fc. Elsevier"},{"key":"ppat.1010255.ref034","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1038\/ni.3563","article-title":"Protective neutralizing influenza antibody response in the absence of T follicular helper cells","volume":"17","author":"K Miyauchi","year":"2016","journal-title":"Nat Immunol"},{"key":"ppat.1010255.ref035","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.immuni.2019.04.011","article-title":"T Follicular Helper Cell Biology: A Decade of Discovery and Diseases","volume":"50","author":"S. Crotty","year":"2019","journal-title":"Immunity"},{"key":"ppat.1010255.ref036","unstructured":"Moderna. Assessment report COVID-19 Vaccine Moderna Common. EMA\/15689\/2021 Corr1*1. 2021;31: 1\u2013169. https:\/\/www.ema.europa.eu\/en\/documents\/assessment-report\/spikevax-previously-covid-19-vaccine-moderna-epar-public-assessment-report_en.pdf"},{"key":"ppat.1010255.ref037","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.immuni.2009.07.005","article-title":"Type I Interferon Signaling in Dendritic Cells Stimulates the Development of Lymph-Node-Resident T Follicular Helper Cells","volume":"31","author":"H Cucak","year":"2009","journal-title":"Immunity"},{"key":"ppat.1010255.ref038","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s13238-015-0210-0","article-title":"Phenotypic Tfh development promoted by CXCR5-controlled re-localization and IL-6 from radiation-resistant cells","volume":"6","author":"X Chen","year":"2015","journal-title":"Protein Cell"},{"key":"ppat.1010255.ref039","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1515\/bmc-2015-0028","article-title":"The dendritic cell side of the immunological synapse","author":"DRJ Verboogen","year":"2016","journal-title":"Biomolecular Concepts. De Gruyter"},{"key":"ppat.1010255.ref040","first-page":"70","article-title":"The dendritic cell synapse: A life dedicated to T cell activation","author":"F. Benvenuti","year":"2016","journal-title":"Frontiers in Immunology"},{"key":"ppat.1010255.ref041","doi-asserted-by":"crossref","first-page":"100924","DOI":"10.1016\/j.mam.2020.100924","article-title":"An overview of the non-canonical inflammasome","volume":"76","author":"KP Downs","year":"2020","journal-title":"Mol Aspects Med"},{"key":"ppat.1010255.ref042","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.immuni.2020.07.026","article-title":"Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses","volume":"53","author":"R Zhou","year":"2020","journal-title":"Immunity"},{"key":"ppat.1010255.ref043","article-title":"Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection","author":"R-E-IM Benhnia","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010255.ref044","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/s41556-021-00681-2","article-title":"Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity","volume":"23","author":"M Saichi","year":"2021","journal-title":"Nat Cell Biol"},{"key":"ppat.1010255.ref045","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.3390\/cells9092046","article-title":"Dendritic Cells and SARS-CoV-2 Infection: Still an Unclarified Connection","volume":"9","author":"P Campana","year":"2020","journal-title":"Cells"},{"key":"ppat.1010255.ref046","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.semcdb.2018.02.020","article-title":"Human dendritic cell immunodeficiencies","author":"V Bigley","year":"2019","journal-title":"Seminars in Cell and Developmental Biology. Semin Cell Dev Biol"},{"key":"ppat.1010255.ref047","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1056\/NEJMc2102131","article-title":"Delayed Large Local Reactions to mRNA-1273 Vaccine against SARS-CoV-2","volume":"384","author":"KG Blumenthal","year":"2021","journal-title":"N Engl J Med"},{"key":"ppat.1010255.ref048","doi-asserted-by":"crossref","first-page":"e2021052478","DOI":"10.1542\/peds.2021-052478","article-title":"Symptomatic Acute Myocarditis in Seven Adolescents Following Pfizer-BioNTech COVID-19 Vaccination","author":"M Marshall","year":"2021","journal-title":"Pediatrics"},{"key":"ppat.1010255.ref049","article-title":"Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military","author":"J Montgomery","year":"2021","journal-title":"JAMA Cardiol"},{"key":"ppat.1010255.ref050","article-title":"Myocarditis Occurring After Immunization With mRNA-Based COVID-19 Vaccines","author":"DK Shay","year":"2021","journal-title":"JAMA Cardiol"},{"key":"ppat.1010255.ref051","doi-asserted-by":"crossref","first-page":"3790","DOI":"10.1016\/j.vaccine.2021.05.087","article-title":"Myocarditis following COVID-19 mRNA vaccination","volume":"39","author":"S Abu Mouch","year":"2021","journal-title":"Vaccine"},{"key":"ppat.1010255.ref052","article-title":"Myocarditis and Pericarditis After Vaccination for COVID-19","author":"GA Diaz","year":"2021","journal-title":"JAMA"},{"key":"ppat.1010255.ref053","article-title":"COVID-19 mRNA vaccination leading to CNS inflammation: a case series","author":"M Khayat-Khoei","year":"2021","journal-title":"J Neurol"},{"key":"ppat.1010255.ref054","article-title":"The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses","author":"FK F\u00f6hse","year":"2021","journal-title":"medRxiv"},{"key":"ppat.1010255.ref055","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/nprot.2009.9","article-title":"Tracking epitope-specific T cells","volume":"4","author":"JJ Moon","year":"2009","journal-title":"Nat Protoc"},{"key":"ppat.1010255.ref056","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1126\/science.1201730","article-title":"Different B cell populations mediate early and late memory during an endogenous immune response","volume":"331","author":"KA Pape","year":"2011","journal-title":"Science"},{"key":"ppat.1010255.ref057","first-page":"85832","article-title":"Vaccine-generated lung tissue-resident memory T cells provide heterosubtypic protection to influenza infection","volume":"1","author":"KD Zens","year":"2016","journal-title":"Ref Inf JCI Insight"},{"key":"ppat.1010255.ref058","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.ajpath.2019.11.003","article-title":"Distinct Chronic Post-Viral Lung Diseases upon Infection with Influenza or Parainfluenza Viruses Differentially Impact Superinfection Outcome","volume":"190","author":"GL Garcia","year":"2020","journal-title":"Am J Pathol"},{"key":"ppat.1010255.ref059","article-title":"Interleukin-6 Knockout Inhibits Senescence of Bone Mesenchymal Stem Cells in High-Fat Diet-Induced Bone Loss","volume":"11","author":"Y Li","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"ppat.1010255.ref060","doi-asserted-by":"crossref","first-page":"8446","DOI":"10.1038\/s41598-018-26603-1","article-title":"The mitochondrial protease HtrA2 restricts the NLRP3 and AIM2 inflammasomes","volume":"8","author":"IG Rodrigue-Gervais","year":"2018","journal-title":"Sci Rep"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010255","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010255","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T13:56:41Z","timestamp":1643896601000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010255"}},"subtitle":[],"editor":[{"given":"Sujan","family":"Shresta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,1,24]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010255","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.08.01.454662","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,24]]}}}