Department of Viroscience, Erasmus University Medical Centre, Rotterdam, The Netherlands.
School of Veterinary Medicine, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana.
PLoS Negl Trop Dis. 2020 Dec 15;14(12):e0008898. doi: 10.1371/journal.pntd.0008898. eCollection 2020 Dec.
Rabies is a fatal neurologic disease caused by lyssavirus infection. Bats are important natural reservoir hosts of various lyssaviruses that can be transmitted to people. The epidemiology and pathogenesis of rabies in bats are poorly understood, making it difficult to prevent zoonotic transmission. To further our understanding of lyssavirus pathogenesis in a natural bat host, an experimental model using straw-colored fruit bats (Eidolon helvum) and Lagos bat virus, an endemic lyssavirus in this species, was developed. To determine the lowest viral dose resulting in 100% productive infection, bats in five groups (four bats per group) were inoculated intramuscularly with one of five doses, ranging from 100.1 to 104.1 median tissue culture infectious dose (TCID50). More bats died due to the development of rabies after the middle dose (102.1 TCID50, 4/4 bats) than after lower (101.1, 2/4; 101.1, 2/4) or higher (103.1, 2/4; 104.1, 2/4) doses of virus. In the two highest dose groups, 4/8 bats developed rabies. Of those bats that remained healthy 3/4 bats seroconverted, suggesting that high antigen loads can trigger a strong immune response that abrogates a productive infection. In contrast, in the two lowest dose groups, 3/8 bats developed rabies, 1/8 remained healthy and seroconverted and 4/8 bats remained healthy and did not seroconvert, suggesting these doses are too low to reliably induce infection. The main lesion in all clinically affected bats was meningoencephalitis associated with lyssavirus-positive neurons. Lyssavirus antigen was detected in tongue epithelium (5/11 infected bats) rather than in salivary gland epithelium (0/11), suggesting viral excretion via the tongue. Thus, intramuscular inoculation of 102.1 TCID50 of Lagos bat virus into straw-colored fruit bats is a suitable model for lyssavirus associated bat rabies in a natural reservoir host, and can help with the investigation of lyssavirus infection dynamics in bats.
狂犬病是一种由狂犬病病毒感染引起的致命性神经疾病。蝙蝠是多种狂犬病病毒的重要自然储存宿主，这些病毒可以传播给人类。由于对蝙蝠狂犬病的流行病学和发病机制了解甚少，因此难以预防人畜共患传播。为了进一步了解天然蝙蝠宿主中狂犬病病毒的发病机制，我们建立了一个使用棕果蝠（Eidolon helvum）和拉各斯蝙蝠病毒（该物种的地方性狂犬病病毒）的实验模型。为了确定导致 100%有产感染的最低病毒剂量，将五组（每组四只蝙蝠）蝙蝠肌肉内接种五种剂量中的一种，范围从 100.1 到 104.1 中组织培养感染剂量（TCID50）。在中间剂量（102.1 TCID50，4/4 只蝙蝠）后，由于狂犬病发展而死亡的蝙蝠比低剂量（101.1，2/4；101.1，2/4）或高剂量（103.1，2/4；104.1，2/4）的病毒后死亡的蝙蝠更多。在两个最高剂量组中，8 只蝙蝠中有 4 只发展为狂犬病。在保持健康的 8 只蝙蝠中，有 3 只产生了血清转化，这表明高抗原负荷可以引发强烈的免疫反应，从而阻止有产感染。相比之下，在两个最低剂量组中，8 只蝙蝠中有 3 只发展为狂犬病，1 只保持健康并产生血清转化，4 只保持健康且未产生血清转化，这表明这些剂量太低，无法可靠地诱导感染。所有临床受影响的蝙蝠的主要病变是与狂犬病病毒阳性神经元相关的脑膜脑炎。在舌上皮（11 只感染蝙蝠中有 5 只）而不是在唾液腺上皮（11 只中 0 只）中检测到狂犬病病毒抗原，这表明病毒通过舌头排出。因此，将 102.1 TCID50 的拉各斯蝙蝠病毒肌肉内接种到棕果蝠中是一种用于天然储主蝙蝠狂犬病的合适模型，可以帮助研究蝙蝠中狂犬病病毒感染的动态。
