Department of Microbiology, Faculty of Medicine, Oita University, Oita, Japan.
Laboratory of Veterinary Public Health, Department of Veterinary Sciences, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.
Microbiol Immunol. 2021 Oct;65(10):438-448. doi: 10.1111/1348-0421.12929. Epub 2021 Aug 3.
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 × 10 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 10 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.
狂犬病是一种由狂犬病病毒（RABV）引起的急性胎儿脑炎。虽然在出现症状后无法治愈，但在潜伏期长的情况下，可以通过暴露后预防（PEP）来预防。虽然临床前诊断有助于适当的 PEP 给药，但由于在潜伏期内没有病毒血症或特定的抗体反应，因此大多数情况下是不可行的。在这里，我们试图确定一种用于狂犬病临床前诊断的血清生物标志物。使用在症状出现前立即通过肌肉内（i.m.）接种 5×10 焦点形成单位（FFU）表达红色荧光素酶的重组 RABV 的感染小鼠的血清（1088/RFLuc），进行二维差异凝胶电泳，然后进行质谱分析，证实载脂蛋白 A1（ApoA1）上调。ELISA 显示，在潜伏期和症状出现当天，血清 ApoA1 和特异性抗体水平增加。由于较低的感染剂量可以用来诱导在自然感染中通常观察到的不稳定和长潜伏期，因此通过体内成像监测病毒动力学来检查肌肉内接种 1088/RFLuc 的 10 个 FFU 的 10 个的小鼠的 ApoA1 水平。在表现出强烈 RABV 复制的小鼠中，血清 ApoA1 和特异性抗体水平分别上调了 50%和 58.3%，但在表现出弱 RABV 复制的小鼠中没有上调。此外，据报道，ApoA1 被发现是神经元损伤的生物标志物。需要更多的生物标志物候选物来有效进行狂犬病的临床前诊断。
