{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:58:18Z","timestamp":1791655098580,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012728","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000}}],"reference-count":92,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI171289-01"],"award-info":[{"award-number":["1R01AI171289-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI007538"],"award-info":[{"award-number":["T32AI007538"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI007538"],"award-info":[{"award-number":["T32AI007538"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Pathogenic hantaviruses are maintained world-wide within wild, asymptomatic rodent reservoir hosts, with increasingly frequent human spillover infections resulting in severe hemorrhagic fever or cardio-pulmonary disease. With no approved therapeutics or vaccines, research has, until recently, focused on understanding the drivers of immune-mediated pathogenesis. An emerging body of work is now investigating the mechanisms that allow for asymptomatic, persistent infections of mammalian reservoir hosts with highly pathogenic RNA viruses. Despite limited experimental data, several hypotheses have arisen to explain limited or absent disease pathology in reservoir hosts. In this study, we directly tested two leading hypotheses: 1) that reservoir host cells induce a generally muted response to viral insults, and 2) that these viruses employ host-specific mechanisms of innate antiviral antagonism to limit immune activation in reservoir cells. We demonstrate that, in contrast to human endothelial cells which mount a robust antiviral and inflammatory response to pathogenic hantaviruses, primary Norway rat endothelial cells do not induce antiviral gene expression in response to infection with their endemic hantavirus, Seoul orthohantavirus (SEOV). Reservoir rat cells do, however, induce strong innate immune responses to exogenous stimulatory RNAs, type I interferon, and infection with Hantaan virus, a closely related hantavirus for which the rat is not a natural reservoir. We also find that SEOV-infected rat endothelial cells remain competent for immune activation induced by exogenous stimuli or subsequent viral infection. Importantly, these findings support an alternative model for asymptomatic persistence within hantavirus reservoir hosts: that efficient viral replication within reservoir host cells may prevent the exposure of critical motifs for cellular antiviral recognition and thus limits immune activation that would otherwise result in viral clearance and\/or immune-mediated disease. Defining the mechanisms that allow for infection tolerance and persistence within reservoir hosts will reveal novel strategies for viral countermeasures against these highly pathogenic zoonotic threats.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012728","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T13:47:51Z","timestamp":1732542471000},"page":"e1012728","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Seoul orthohantavirus evades innate immune activation by reservoir endothelial cells"],"prefix":"10.1371","volume":"20","author":[{"given":"Stefan D.","family":"Klimaj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Autumn","family":"LaPointe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Hernandez","family":"Acosta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5550-1038","authenticated-orcid":true,"given":"Alison M.","family":"Kell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"issue":"3","key":"ppat.1012728.ref001","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s11538-005-9034-4","article-title":"Mathematical models for hantavirus infection in rodents","volume":"68","author":"LJ Allen","year":"2006","journal-title":"Bulletin of mathematical biology"},{"issue":"4","key":"ppat.1012728.ref002","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.jtbi.2009.07.009","article-title":"A habitat-based model for the spread of hantavirus between reservoir and spillover species","volume":"260","author":"LJ Allen","year":"2009","journal-title":"Journal of theoretical biology"},{"issue":"2","key":"ppat.1012728.ref003","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1128\/CMR.00062-09","article-title":"A global perspective on hantavirus ecology, epidemiology, and disease.","volume":"23","author":"CB Jonsson","year":"2010","journal-title":"Clin Microbiol Rev."},{"issue":"22","key":"ppat.1012728.ref004","doi-asserted-by":"crossref","first-page":"7039","DOI":"10.1073\/pnas.1501598112","article-title":"Rodent reservoirs of future zoonotic diseases","volume":"112","author":"BA Han","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"ppat.1012728.ref005","article-title":"Sin Nombre Virus and the Emergence of Other Hantaviruses: A Review of the Biology, Ecology, and Disease of a Zoonotic Pathogen.","volume":"12","author":"AT Jacob","year":"2023","journal-title":"Biology (Basel)."},{"key":"ppat.1012728.ref006","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.semcdb.2016.07.002","article-title":"Infection resistance and tolerance in Peromyscus spp., natural reservoirs of microbes that are virulent for humans","volume":"61","author":"AG Barbour","year":"2017","journal-title":"Semin Cell Dev Biol"},{"issue":"2","key":"ppat.1012728.ref007","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00588-21","article-title":"An Infection-Tolerant Mammalian Reservoir for Several Zoonotic Agents Broadly Counters the Inflammatory Effects of Endotoxin.","volume":"12","author":"G Balderrama-Gutierrez","year":"2021","journal-title":"mBio"},{"issue":"8","key":"ppat.1012728.ref008","doi-asserted-by":"crossref","DOI":"10.3390\/v13081620","article-title":"Comparative Computational Modeling of the Bat and Human Immune Response to Viral Infection with the Comparative Biology Immune Agent Based Model.","volume":"13","author":"C Cockrell","year":"2021","journal-title":"Viruses"},{"issue":"5\u20136","key":"ppat.1012728.ref009","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1600-0684.2005.00122.x","article-title":"Naturally SIV-infected sooty mangabeys: are we closer to understanding why they do not develop AIDS","volume":"34","author":"G. 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Koskela","year":"2021","journal-title":"Viruses."},{"issue":"8","key":"ppat.1012728.ref033","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1016\/j.celrep.2019.07.066","article-title":"Hantavirus Inhibits TRAIL-Mediated Killing of Infected Cells by Downregulating Death Receptor 5.","volume":"28","author":"C Sol\u00e0-Riera","year":"2019","journal-title":"Cell Rep."},{"issue":"1","key":"ppat.1012728.ref034","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/s41598-018-37446-1","article-title":"Orthohantaviruses belonging to three phylogroups all inhibit apoptosis in infected target cells","volume":"9","author":"C Sol\u00e0-Riera","year":"2019","journal-title":"Sci Rep"},{"issue":"2","key":"ppat.1012728.ref035","doi-asserted-by":"crossref","first-page":"e1008297","DOI":"10.1371\/journal.ppat.1008297","article-title":"Hantavirus inhibits apoptosis by preventing mitochondrial membrane potential loss through up-regulation of the pro-survival factor 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Xiao","year":"1994","journal-title":"Virology"},{"key":"ppat.1012728.ref063","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2016.11.002","article-title":"Amending Koch\u2019s postulates for viral disease: When \"growth in pure culture\" leads to a loss of virulence.","volume":"137","author":"J Prescott","year":"2017","journal-title":"Antiviral Res"},{"issue":"12","key":"ppat.1012728.ref064","doi-asserted-by":"crossref","first-page":"9515","DOI":"10.1128\/jvi.71.12.9515-9523.1997","article-title":"Cell culture adaptation of Puumala hantavirus changes the infectivity for its natural reservoir, Clethrionomys glareolus, and leads to accumulation of mutants with altered genomic RNA S segment","volume":"71","author":"A Lundkvist","year":"1997","journal-title":"Journal of virology"},{"issue":"1","key":"ppat.1012728.ref065","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1128\/JVI.01796-07","article-title":"3\u2019 RNA elements in hepatitis C virus 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Kato","year":"2005","journal-title":"Immunity"},{"issue":"48","key":"ppat.1012728.ref069","doi-asserted-by":"crossref","first-page":"5713","DOI":"10.1016\/j.vaccine.2013.09.040","article-title":"Highly immunostimulatory RNA derived from a Sendai virus defective viral genome","volume":"31","author":"X Mercado-Lopez","year":"2013","journal-title":"Vaccine"},{"issue":"5","key":"ppat.1012728.ref070","first-page":"e01265","article-title":"Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I.","volume":"6","author":"J Xu","year":"2015","journal-title":"mBio"},{"issue":"7","key":"ppat.1012728.ref071","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.tim.2020.02.006","article-title":"Defective Interfering Particles of Negative-Strand RNA Viruses","volume":"28","author":"CM Ziegler","year":"2020","journal-title":"Trends Microbiol"},{"issue":"7","key":"ppat.1012728.ref072","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1038\/s41564-019-0465-y","article-title":"Defective viral genomes are key drivers of the virus-host interaction.","volume":"4","author":"M Vignuzzi","year":"2019","journal-title":"Nat Microbiol"},{"issue":"2","key":"ppat.1012728.ref073","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1177\/147323001204000227","article-title":"Elevated serum concentrations of inflammatory cytokines and chemokines in patients with haemorrhagic fever with renal syndrome","volume":"40","author":"PZ Wang","year":"2012","journal-title":"The Journal of international medical research"},{"issue":"13","key":"ppat.1012728.ref074","doi-asserted-by":"crossref","first-page":"7178","DOI":"10.1128\/JVI.00254-14","article-title":"Neutrophil depletion suppresses pulmonary vascular hyperpermeability and occurrence of pulmonary edema caused by hantavirus infection in C.B-17 SCID mice","volume":"88","author":"T Koma","year":"2014","journal-title":"Journal of virology"},{"issue":"5","key":"ppat.1012728.ref075","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.coviro.2012.08.001","article-title":"Virus population bottlenecks during within-host progression and host-to-host transmission.","volume":"2","author":"S Guti\u00e9rrez","year":"2012","journal-title":"Curr Opin Virol"},{"issue":"3","key":"ppat.1012728.ref076","doi-asserted-by":"crossref","first-page":"e0012074","DOI":"10.1371\/journal.pntd.0012074","article-title":"Species-specific responses during Seoul orthohantavirus infection in human and rat lung microvascular endothelial cells.","volume":"18","author":"D Noack","year":"2024","journal-title":"PLoS Negl Trop Dis"},{"issue":"10","key":"ppat.1012728.ref077","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1016\/j.cell.2023.03.036","article-title":"Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases","volume":"186","author":"M Ahn","year":"2023","journal-title":"Cell"},{"key":"ppat.1012728.ref078","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.virusres.2014.01.008","article-title":"Evolution of hantaviruses: co-speciation with reservoir hosts for more than 100 MYR","volume":"187","author":"A Plyusnin","year":"2014","journal-title":"Virus Res"},{"issue":"15","key":"ppat.1012728.ref079","doi-asserted-by":"crossref","first-page":"7587","DOI":"10.1128\/JVI.76.15.7587-7594.2002","article-title":"Shedding and intracage transmission of Sin Nombre hantavirus in the deer mouse (Peromyscus maniculatus) model.","volume":"76","author":"J Botten","year":"2002","journal-title":"J Virol"},{"issue":"3","key":"ppat.1012728.ref080","doi-asserted-by":"crossref","first-page":"e1005501","DOI":"10.1371\/journal.ppat.1005501","article-title":"The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles.","volume":"12","author":"CM Ziegler","year":"2016","journal-title":"PLoS Pathog"},{"issue":"7","key":"ppat.1012728.ref081","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2217\/fvl-2018-0021","article-title":"Defective (interfering) viral genomes re-explored: impact on antiviral immunity and virus persistence.","volume":"13","author":"TB Manzoni","year":"2018","journal-title":"Future Virol"},{"issue":"6630","key":"ppat.1012728.ref082","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1126\/science.ade9733","article-title":"Infection infidelities drive innate immunity","volume":"379","author":"JC Kagan","year":"2023","journal-title":"Science"},{"issue":"7","key":"ppat.1012728.ref083","doi-asserted-by":"crossref","DOI":"10.3390\/cells9071569","article-title":"The RNA Replication Site of Tula Orthohantavirus Resides within a Remodelled Golgi Network.","volume":"9","author":"KA Davies","year":"2020","journal-title":"Cells"},{"issue":"9","key":"ppat.1012728.ref084","doi-asserted-by":"crossref","first-page":"5754","DOI":"10.1128\/jvi.69.9.5754-5762.1995","article-title":"The 5\u2019 ends of Hantaan virus (Bunyaviridae) RNAs suggest a prime-and-realign mechanism for the initiation of RNA synthesis.","volume":"69","author":"D Garcin","year":"1995","journal-title":"J Virol"},{"issue":"4","key":"ppat.1012728.ref085","doi-asserted-by":"crossref","first-page":"e2032","DOI":"10.1371\/journal.pone.0002032","article-title":"Processing of genome 5\u2019 termini as a strategy of negative-strand RNA viruses to avoid RIG-I-dependent interferon induction.","volume":"3","author":"M Habjan","year":"2008","journal-title":"PLoS One."},{"issue":"5801","key":"ppat.1012728.ref086","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1126\/science.1132505","article-title":"5\u2019-Triphosphate RNA is the ligand for RIG-I","volume":"314","author":"V Hornung","year":"2006","journal-title":"Science"},{"issue":"8","key":"ppat.1012728.ref087","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nmeth.3047","volume":"11","author":"NE Sanjana","year":"2014","journal-title":"Nat Methods"},{"issue":"7","key":"ppat.1012728.ref088","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1084\/jem.20081210","article-title":"Jr. Differential recognition of double-stranded RNA by RIG-I-like receptors in antiviral immunity","volume":"205","author":"T Saito","year":"2008","journal-title":"The Journal of experimental medicine"},{"issue":"8","key":"ppat.1012728.ref089","first-page":"e1002839","volume":"8","author":"G Schnell","year":"2012","journal-title":"Jr. Uridine composition of the poly-U\/UC tract of HCV RNA defines non-self recognition by RIG-I. PLoS pathogens"},{"issue":"21","key":"ppat.1012728.ref090","doi-asserted-by":"crossref","first-page":"11056","DOI":"10.1128\/JVI.01964-15","article-title":"Pathogen-Associated Molecular Pattern Recognition of Hepatitis C Virus Transmitted\/Founder Variants by RIG-I Is Dependent on U-Core Length","volume":"89","author":"A Kell","year":"2015","journal-title":"J Virol"},{"issue":"8","key":"ppat.1012728.ref091","doi-asserted-by":"crossref","first-page":"2986","DOI":"10.1073\/pnas.0408707102","article-title":"Control of antiviral defenses through hepatitis C virus disruption of retinoic acid-inducible gene-I signaling.","volume":"102","author":"E Foy","year":"2005","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ppat.1012728.ref092","volume-title":"Seoul orthohantavirus evades innate immune activation by reservoir endothelial cells; 2024 [cited 2024 Oct 25].","author":"AM Kell"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1012728","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012728","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T13:44:04Z","timestamp":1733751844000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012728"}},"subtitle":[],"editor":[{"given":"Sabra L.","family":"Klein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,25]]},"references-count":92,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012728","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.06.18.599607","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,25]]}}}