As feared and deadly human diseases globally, Rabies virus contrived mechanisms to escape early immune recognition via suppression of the interferon response. This study, preliminarily investigated whether Rabies virus employs epigenetic mechanism for the suppression of the interferon using the Challenge virus standard (CVS) strain and Nigerian street Rabies virus (SRV) strain. Mice were challenged with Rabies virus (RABV) infection, and presence of RABV antigen was assessed by direct fluorescent antibody test (DFAT). A real time quantitative Polymerase chain reaction (qRT-PCR) was used to measure the expression of type II interferon gamma (IFNG) and methylation specific quantitative PCR for methylation analysis of 1FNG promoter region. Accordingly, DNA methyltransferase (DNMT) and histone acetyltransferase (HAT) enzymes activities were determined. RABV antigen was detected in all infected samples. A statistically significant increase (p < 0.05) in mRNA level of IFNG was observed at the onset of the disease and a decrease as the disease progressed. An increase in methylation in the test groups from the control group was observed, with a fluctuation in methylation as the disease progressed. DNMT and HAT activities also agree with methylation as there was an observed increase activity in test group compared with control group. Similar fluctuation pattern was observed in both CVS and SRV groups as the disease progressed with HAT, being the most active proportionally. This study suggests that epigenetic modification via DNA methylation and histone acetylation may have played a role in the expression of type II interferon gamma in Rabies virus infection. Graphical abstract.

中文翻译：

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在小鼠脑中诱导狂犬病病毒感染可能通过表观遗传修饰上调和下调 II 型干扰素 γ。

作为全球范围内令人恐惧和致命的人类疾病，狂犬病病毒设计了通过抑制干扰素反应来逃避早期免疫识别的机制。本研究使用挑战病毒标准（CVS）毒株和尼日利亚街头狂犬病病毒（SRV）毒株，初步研究了狂犬病病毒是否采用表观遗传机制抑制干扰素。小鼠受到狂犬病病毒 (RABV) 感染的攻击，并通过直接荧光抗体测试 (DFAT) 评估 RABV 抗原的存在。实时定量聚合酶链反应 (qRT-PCR) 用于测量 II 型干扰素 γ (IFNG) 的表达和甲基化特异性定量 PCR 用于 1FNG 启动子区域的甲基化分析。因此，测定了 DNA 甲基转移酶 (DNMT) 和组蛋白乙酰转移酶 (HAT) 酶活性。在所有感染样本中均检测到 RABV 抗原。在疾病开始时观察到 IFNG mRNA 水平的统计学显着增加 (p < 0.05)，并随着疾病进展而降低。观察到与对照组相比，测试组的甲基化增加，随着疾病的进展甲基化出现波动。DNMT 和 HAT 活性也与甲基化一致，因为与对照组相比，在测试组中观察到活性增加。随着 HAT 的进展，在 CVS 和 SRV 组中观察到类似的波动模式，是最活跃的比例。这项研究表明，通过 DNA 甲基化和组蛋白乙酰化进行的表观遗传修饰可能在狂犬病病毒感染中 II 型干扰素 γ 的表达中发挥了作用。图形概要。