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While it becomes incurable after symptom onset, it can be prevented by post\u2010exposure prophylaxis (PEP) during the long incubation period. While preclinical diagnosis aids the appropriate PEP administration, it is mostly nonfeasible owing to the absence of viremia or a specific antibody response during the incubation period. Here, an attempt was made to identify a serum biomarker for the preclinical diagnosis of rabies. Using the serum from a mouse inoculated intramuscularly (i.m.) with 5\u2009\u00d7\u200910<jats:sup>5<\/jats:sup> focus\u2010forming units (FFU) of recombinant RABV expressing red firefly luciferase (1088\/RFLuc) immediately before symptom onset, two\u2010dimensional differential gel electrophoresis was conducted, followed by mass spectrometry, and it was confirmed that apolipoprotein A1 (ApoA1) was up\u2010regulated. ELISA showed that the serum ApoA1 and specific antibody levels increased during the incubation period and on the day of symptom onset. Since a lower infectious dose can be used to induce the unstable and long incubation period generally observed in natural infection, the ApoA1 level in mice inoculated i.m. with 10<jats:sup>3<\/jats:sup>\u2009FFU of 1088\/RFLuc was examined by monitoring viral dynamics using in vivo imaging. The serum ApoA1 and specific antibody levels were up\u2010regulated in 50% and 58.3% of mice exhibiting robust RABV replication, respectively, but not in mice exhibiting weak RABV replication. In addition, it was reported that ApoA1 was found to be a biomarker for neuronal damage. Additional biomarker candidates will be needed for the effective preclinical diagnosis of rabies.<\/jats:p>","DOI":"10.1111\/1348-0421.12929","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T13:25:22Z","timestamp":1626441922000},"page":"438-448","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Validation of serum apolipoprotein A1 in rabies virus\u2010infected mice as a biomarker for the preclinical diagnosis of rabies"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5454-4554","authenticated-orcid":false,"given":"Kentaro","family":"Yamada","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Oita University Oita Japan"},{"name":"Laboratory of Veterinary Public Health, Department of Veterinary Sciences, Faculty of Agriculture University of Miyazaki Miyazaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Kuribayashi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Oita University Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naotaka","family":"Inomata","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Oita University Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuko","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Oita University Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7203-0466","authenticated-orcid":false,"given":"Kazunori","family":"Kimitsuki","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Oita University Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9212-1429","authenticated-orcid":false,"given":"Catalino S.","family":"Demetria","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Oita University Oita Japan"},{"name":"Veterinary Research Department Research Institute for Tropical Medicine Muntinlupa City Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4396-5000","authenticated-orcid":false,"given":"Nobuo","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Oita University Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science National Institute of Infectious Diseases Tokyo Japan"},{"name":"Department of Veterinary Pathology, School of Veterinary Medicine Kitasato University Aomori Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun\u2010Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, School of Veterinary Medicine Kitasato University Aomori Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Kaimori","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Oita University Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8340-0880","authenticated-orcid":false,"given":"Motoi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Infectious Disease Surveillance Center National Institute of Infectious Diseases Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariko","family":"Saito\u2010Obata","sequence":"additional","affiliation":[{"name":"Department of Virology Tohoku University Graduate School of Medicine  Miyagi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7190-1082","authenticated-orcid":false,"given":"Yasuhiko","family":"Kamiya","sequence":"additional","affiliation":[{"name":"School of Tropical Medicine &amp; Global Health Nagasaki University Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daria L.","family":"Manalo","sequence":"additional","affiliation":[{"name":"Veterinary Research Department Research Institute for Tropical Medicine Muntinlupa City Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2916-3199","authenticated-orcid":false,"given":"Beatriz P.","family":"Quiambao","sequence":"additional","affiliation":[{"name":"Research Institute for Tropical Medicine Muntinlupa City Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1364-4839","authenticated-orcid":false,"given":"Akira","family":"Nishizono","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Oita University Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.91"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-818705-0.00004-2"},{"key":"e_1_2_9_4_1","unstructured":"World Health Organization.WHO expert consultation on rabies: third report. 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