{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:02:46Z","timestamp":1788447766650,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key R&amp;D Program of China","award":["2021YFC2301700"],"award-info":[{"award-number":["2021YFC2301700"]}]},{"name":"National Key R&amp;D Program of China","award":["2017ZX103304402"],"award-info":[{"award-number":["2017ZX103304402"]}]},{"name":"National Science and Technology Major Projects of Infectious Disease funds","award":["2021YFC2301700"],"award-info":[{"award-number":["2021YFC2301700"]}]},{"name":"National Science and Technology Major Projects of Infectious Disease funds","award":["2017ZX103304402"],"award-info":[{"award-number":["2017ZX103304402"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Intensive efforts have been made to develop models of hRSV infection or disease using various animals. However, the limitations such as semi-permissiveness and short duration of infection have impeded their applications in both the pathogenesis of hRSV and therapeutics development. Here, we present a mouse model based on a Rag2 gene knockout using CRISPR\/Cas9 technology. Rag2\u2212\/\u2212 mice sustained high viral loads upon intranasal inoculation with hRSV. The average peak titer rapidly reached 1 \u00d7 109.8 copies\/g and 1c106 TCID50 in nasal cavity, as well as 1 \u00d7 108 copies\/g and 1 \u00d7 105 TCID50 in the lungs up to 5 weeks. Mild interstitial pneumonia, severe bronchopneumonia, elevated cytokines and NK cells were seen in Rag2\u2212\/\u2212 mice. A humanized monoclonal antibody showed strong antiviral activity in this animal model, implying that Rag2\u2212\/\u2212 mice that support long-term stable infection are a useful tool for studying the transmission and pathogenesis of human RSV, as well as evaluating therapeutics.<\/jats:p>","DOI":"10.3390\/v14081740","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T09:47:06Z","timestamp":1660124826000},"page":"1740","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Long-Term Infection and Pathogenesis in a Novel Mouse Model of Human Respiratory Syncytial Virus"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0126-0563","authenticated-orcid":false,"given":"Rui","family":"Xiong","sequence":"first","affiliation":[{"name":"National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China"},{"name":"Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Fu","sequence":"additional","affiliation":[{"name":"National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wu","sequence":"additional","affiliation":[{"name":"National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wu","sequence":"additional","affiliation":[{"name":"National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Cao","sequence":"additional","affiliation":[{"name":"National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Qu","sequence":"additional","affiliation":[{"name":"National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control (NIFDC), Beijing 100176, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwei","family":"Yang","sequence":"additional","affiliation":[{"name":"National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control (NIFDC), Beijing 100176, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susu","family":"Liu","sequence":"additional","affiliation":[{"name":"National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guitao","family":"Huo","sequence":"additional","affiliation":[{"name":"National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control (NIFDC), Beijing 100176, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanlong","family":"Wang","sequence":"additional","affiliation":[{"name":"National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control (NIFDC), Beijing 100176, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4246-8889","authenticated-orcid":false,"given":"Weijin","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS and Sexually Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Pathology, InnoStar Bio-Tech Nantong Co., Ltd., Nantong 226133, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6850-1950","authenticated-orcid":false,"given":"Chunnan","family":"Liang","sequence":"additional","affiliation":[{"name":"National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3603-8014","authenticated-orcid":false,"given":"Yihong","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-5141","authenticated-orcid":false,"given":"Youchun","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of 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