{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T21:27:36Z","timestamp":1787866056116,"version":"build-2784847793"},"posted":{"date-parts":[[2026,8,25]]},"group-title":"Microbiology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"U.S. National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["HHSN272201800013C"],"award-info":[{"award-number":["HHSN272201800013C"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["75N91019D00024"],"award-info":[{"award-number":["75N91019D00024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Development of candidate countermeasures against human pathogens frequently includes nonhuman animal experimentation. Preclinical animal pathogen exposure studies are conducted to model diseases and accumulate preliminary and hypothetically translatable data to inform and justify the design of clinical trial evaluation of countermeasure safety and efficacy. In addition to frequent ethical critiques, challenges associated with animal experimentation include considerable resources needed to achieve statistical power and robustness, replicability and reproducibility concerns, potentially compromised objectivity through lack of blinding, fundamental species-specific biological differences, and risk of unpredictable pathogen adaptation to the experimental animal. Recent U.S. and U.K. government initiatives aim to reduce animal experimentation by complementing or potentially replacing them with new approach methodologies (NAMs), i.e., increasingly sophisticated\n                  <jats:italic>in silico<\/jats:italic>\n                  ,\n                  <jats:italic>in chemico<\/jats:italic>\n                  , and\n                  <jats:italic>in vitro<\/jats:italic>\n                  approaches. We piloted development of one type of NAM, organ-on-chips (OOCs), in the highly challenging environment of a maximum (biosafety level 4) containment laboratory. Using a Risk Group 4 virus, Nipah virus (NiV), and two types of lung OOCs seeded with human or porcine cells, we demonstrated the recapitulation of key features of NiV lung infection, including viral infection, replication, and translocation, that are associated with proinflammatory cytokine secretion, immune cell recruitment, and disruption of the air\u2013liquid interface barrier. We reproduced the known anti-NiV activity of remdesivir and evaluated that of another potential antiviral, zotatifin. Our results pave the way for similar applications of advanced microphysiological systems for modeling infections caused by high-consequence viruses.\n                <\/jats:p>","DOI":"10.64898\/2026.08.24.745299","type":"posted-content","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T03:55:31Z","timestamp":1787716531000},"source":"Crossref","is-referenced-by-count":0,"title":["Modeling Risk Group 4 virus infection and antiviral treatment in microfluidic lung organ-on-chips in maximum containment laboratories"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4356-4239","authenticated-orcid":false,"given":"Sushma M.","family":"Bhosle","sequence":"first","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4162-1271","authenticated-orcid":false,"given":"Julie P.","family":"Tran","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9473-566X","authenticated-orcid":false,"given":"Shuiqing","family":"Yu","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3537-3945","authenticated-orcid":false,"given":"Jillian","family":"Geiger","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5878-7091","authenticated-orcid":false,"given":"Arpita","family":"Das","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1590-7401","authenticated-orcid":false,"given":"Scott M.","family":"Anthony","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1949-973X","authenticated-orcid":false,"given":"Bapi","family":"Pahar","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6554-9000","authenticated-orcid":false,"given":"Rebecca","family":"Bernbaum-Cutler","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8221-4480","authenticated-orcid":false,"given":"Deja F. P.","family":"Rivera","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2485-4011","authenticated-orcid":false,"given":"Ian","family":"Crozier","sequence":"additional","affiliation":[{"name":"Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9846-0846","authenticated-orcid":false,"given":"Jiro","family":"Wada","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2060-2469","authenticated-orcid":false,"given":"Anya","family":"Crane","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5062-1938","authenticated-orcid":false,"given":"Gustavo","family":"Palacios","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Global Health Emerging Pathogens Institute, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7914-3682","authenticated-orcid":false,"given":"Nicole C.","family":"Kleinstreuer","sequence":"additional","affiliation":[{"name":"Division of Program Coordination, Planning, and Strategic Initiatives, National Institutes of Health, Research Triangle Park, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7800-6045","authenticated-orcid":false,"given":"Jens H.","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7485-2204","authenticated-orcid":false,"given":"Gabriella","family":"Worwa","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026082714150614000_2026.08.24.745299v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3697"},{"key":"2026082714150614000_2026.08.24.745299v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.01.010"},{"key":"2026082714150614000_2026.08.24.745299v1.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504887102"},{"key":"2026082714150614000_2026.08.24.745299v1.4","doi-asserted-by":"publisher","DOI":"10.3201\/eid1812.120875"},{"key":"2026082714150614000_2026.08.24.745299v1.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005532"},{"key":"2026082714150614000_2026.08.24.745299v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2020.11.009"},{"key":"2026082714150614000_2026.08.24.745299v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e26503"},{"key":"2026082714150614000_2026.08.24.745299v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz455"},{"key":"2026082714150614000_2026.08.24.745299v1.9","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-7-305"},{"key":"2026082714150614000_2026.08.24.745299v1.10","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000441"},{"key":"2026082714150614000_2026.08.24.745299v1.11","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00275-17"},{"key":"2026082714150614000_2026.08.24.745299v1.12","unstructured":"Food and Drug Administration. 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