TY - JOUR
T1 - Validation of serum apolipoprotein A1 in rabies virus-infected mice as a biomarker for the preclinical diagnosis of rabies
AU - Yamada, Kentaro
AU - Kuribayashi, Koji
AU - Inomata, Naotaka
AU - Noguchi, Kazuko
AU - Kimitsuki, Kazunori
AU - Demetria, Catalino S.
AU - Saito, Nobuo
AU - Inoue, Satoshi
AU - Park, Chun Ho
AU - Kaimori, Ryo
AU - Suzuki, Motoi
AU - Saito-Obata, Mariko
AU - Kamiya, Yasuhiko
AU - Manalo, Daria L.
AU - Quiambao, Beatriz P.
AU - Nishizono, Akira
N1 - Funding Information:
We thank Ms Mami Koya (Oita University) for helping us to conduct 2D‐DIGE and protein identification experiments. We also thank Dr Kazuaki Mannen (Oita University) for providing the High Five cells. This work was supported by Science and Technology Research Partnership for Sustainable Development (SATREPS), Japan Agency for Medical Research and Development (AMED)/JICA to Akira Nishizono (No. 17823721).
Publisher Copyright:
© 2021 The Authors. Microbiology and Immunology published by The Societies and John Wiley & Sons Australia, Ltd
PY - 2021/10
Y1 - 2021/10
N2 - Rabies is a type of acute fetal encephalitis caused by rabies virus (RABV). While it becomes incurable after symptom onset, it can be prevented by post-exposure 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 × 105 focus-forming units (FFU) of recombinant RABV expressing red firefly luciferase (1088/RFLuc) immediately before symptom onset, two-dimensional differential gel electrophoresis was conducted, followed by mass spectrometry, and it was confirmed that apolipoprotein A1 (ApoA1) was up-regulated. 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 103 FFU of 1088/RFLuc was examined by monitoring viral dynamics using in vivo imaging. The serum ApoA1 and specific antibody levels were up-regulated 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.
AB - Rabies is a type of acute fetal encephalitis caused by rabies virus (RABV). While it becomes incurable after symptom onset, it can be prevented by post-exposure 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 × 105 focus-forming units (FFU) of recombinant RABV expressing red firefly luciferase (1088/RFLuc) immediately before symptom onset, two-dimensional differential gel electrophoresis was conducted, followed by mass spectrometry, and it was confirmed that apolipoprotein A1 (ApoA1) was up-regulated. 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 103 FFU of 1088/RFLuc was examined by monitoring viral dynamics using in vivo imaging. The serum ApoA1 and specific antibody levels were up-regulated 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.
KW - ApoA1
KW - biomarker
KW - in vivo imaging
KW - proteomics
KW - rabies
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U2 - 10.1111/1348-0421.12929
DO - 10.1111/1348-0421.12929
M3 - Article
C2 - 34270107
AN - SCOPUS:85111852333
VL - 65
SP - 438
EP - 448
JO - Microbiology and Immunology
JF - Microbiology and Immunology
SN - 0385-5600
IS - 10
ER -