{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:08:10Z","timestamp":1791443290498,"version":"4.3.3"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"NIH","award":["R21AI113206-01"],"award-info":[{"award-number":["R21AI113206-01"]}]},{"name":"Galveston National Laboratory","award":["5UC7AI094660-05"],"award-info":[{"award-number":["5UC7AI094660-05"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures for persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model of MERS-CoV infection and disease that globally expresses human CD26 (hCD26)\/DPP4. The 50% infectious dose (ID\n                    <jats:sub>50<\/jats:sub>\n                    ) and lethal dose (LD\n                    <jats:sub>50<\/jats:sub>\n                    ) of virus were estimated to be &lt;1 and 10 TCID\n                    <jats:sub>50<\/jats:sub>\n                    of MERS-CoV, respectively. Neutralizing antibody developed in the surviving mice from the ID\n                    <jats:sub>50<\/jats:sub>\n                    \/LD\n                    <jats:sub>50<\/jats:sub>\n                    determinations, and all were fully immune to challenge with 100 LD\n                    <jats:sub>50<\/jats:sub>\n                    of MERS-CoV. The tissue distribution and histopathology in mice challenged with a potential working dose of 10 LD\n                    <jats:sub>50<\/jats:sub>\n                    of MERS-CoV were subsequently evaluated. In contrast to the overwhelming infection seen in the mice challenged with 10\n                    <jats:sup>5<\/jats:sup>\n                    LD\n                    <jats:sub>50<\/jats:sub>\n                    of MERS-CoV, we were able to recover infectious virus from these mice only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early and persistent lung infection and delayed occurrence of brain infection. Persistent inflammatory infiltrates were seen in the lungs and brain stems at day 2 and day 6 after infection, respectively. While focal infiltrates were also noted in the liver, definite pathology was not seen in other tissues. Finally, using a receptor binding domain protein vaccine and a MERS-CoV fusion inhibitor, we demonstrated the value of this model for evaluating vaccines and antivirals against MERS. As outcomes of MERS-CoV infection in patients differ greatly, ranging from asymptomatic to overwhelming disease and death, having available both an infection model and a lethal model makes this transgenic mouse model relevant for advancing MERS research.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    Fully characterized animal models are essential for studying pathogenesis and for preclinical screening of vaccines and drugs against MERS-CoV infection and disease. When given a high dose of MERS-CoV, our transgenic mice expressing hCD26\/DPP4 viral receptor uniformly succumbed to death within 6 days, making it difficult to evaluate host responses to infection and disease. We further characterized this model by determining both the ID\n                    <jats:sub>50<\/jats:sub>\n                    and the LD\n                    <jats:sub>50<\/jats:sub>\n                    of MERS-CoV in order to establish both an infection model and a lethal model for MERS and followed this by investigating the antibody responses and immunity of the mice that survived MERS-CoV infection. Using the estimated LD\n                    <jats:sub>50<\/jats:sub>\n                    and ID\n                    <jats:sub>50<\/jats:sub>\n                    data, we dissected the kinetics of viral tissue distribution and pathology in mice challenged with 10 LD\n                    <jats:sub>50<\/jats:sub>\n                    of virus and utilized the model for preclinical evaluation of a vaccine and drug for treatment of MERS-CoV infection. This further-characterized transgenic mouse model will be useful for advancing MERS research.\n                  <\/jats:p>","DOI":"10.1128\/jvi.02009-15","type":"journal-article","created":{"date-parts":[[2015,10,7]],"date-time":"2015-10-07T22:18:53Z","timestamp":1444256333000},"page":"57-67","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":77,"title":["Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease"],"prefix":"10.1128","volume":"90","author":[{"given":"Xinrong","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Garron","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anurodh Shankar","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Algaissi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi-Hung","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Wakamiya","sequence":"additional","affiliation":[{"name":"Transgenic Mouse Core Facility, Institute for Translational Sciences and Animal Resource Center, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teh-Sheng","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanying","family":"Du","sequence":"additional","affiliation":[{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Couch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Disease, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Te K.","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1143"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306742"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60982-4"},{"key":"e_1_3_2_5_2","volume-title":"MERS-CoV risk assessment","author":"World Health Organization","year":"2015","unstructured":"World Health Organization. 3 June 2015. Summary and risk assessment of current situation in Korea and China. MERS-CoV risk assessment. World Health Organization, Geneva, Switzerland. http:\/\/www.who.int\/csr\/disease\/coronavirus_infections\/risk-assessment-3june2015\/en\/."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1310744110"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004250"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.060640-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069127"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02935-13"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03427-14"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1510830112"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1323279111"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081587"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035421"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.08.086"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2015.03"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03001-13"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv325"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2015.1021527"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8712"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02433-13"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4067"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211721"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60454-8"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70154-3"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20040302"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.inf.0000144666.95284.05"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1560"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13413-7"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050828"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1086\/444461"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02012-06"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030005"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01702-06"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-015-0720-y"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiph.2013.06.001"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02009-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02009-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T09:09:29Z","timestamp":1646471369000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.02009-15"}},"subtitle":[],"editor":[{"given":"A.","family":"Garc\u00eda-Sastre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,1]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1128\/JVI.02009-15"],"URL":"https:\/\/doi.org\/10.1128\/jvi.02009-15","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726802322.793535754","asserted-by":"object"}]},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1]]},"assertion":[{"value":"2015-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-10-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}