Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
PLoS Pathog. 2019 Jun 20;15(6):e1007833. doi: 10.1371/journal.ppat.1007833. eCollection 2019 Jun.
Rift Valley fever virus (RVFV) causes severe disease in livestock concurrent with zoonotic transmission to humans. A subset of people infected with RVFV develop encephalitis, and significant gaps remain in our knowledge of how RVFV causes pathology in the brain. We previously found that, in Lewis rats, subcutaneous inoculation with RVFV resulted in subclinical disease while inhalation of RVFV in a small particle aerosol caused fatal encephalitis. Here, we compared the disease course of RVFV in Lewis rats after each different route of inoculation in order to understand more about pathogenic mechanisms of fatal RVFV encephalitis. In aerosol-infected rats with lethal encephalitis, neutrophils and macrophages were the major cell types infiltrating the CNS, and this was concomitant with microglia activation and extensive cytokine inflammation. Despite this, prevention of neutrophil infiltration into the brain did not ameliorate disease. Unexpectedly, in subcutaneously-inoculated rats with subclinical disease, detectable viral RNA was found in the brain along with T-cell infiltration. This study sheds new light on the pathogenic mechanisms of RVFV encephalitis.
裂谷热病毒（RVFV）可引起家畜严重疾病，并发生人间人畜共患传播。感染 RVFV 的一部分人会发生脑炎，而我们对 RVFV 如何引起大脑病理变化的了解仍存在很大差距。我们之前发现，在刘易斯大鼠中，RVFV 的皮下接种导致亚临床疾病，而 RVFV 在小颗粒气溶胶中的吸入则导致致命性脑炎。在这里，我们比较了 RVFV 在不同接种途径后的疾病进程，以更深入地了解致命性 RVFV 脑炎的发病机制。在致命性脑炎的气溶胶感染大鼠中，中性粒细胞和巨噬细胞是浸润中枢神经系统的主要细胞类型，这与小胶质细胞激活和广泛的细胞因子炎症相伴发生。尽管如此，阻止中性粒细胞浸润大脑并不能改善疾病。出乎意料的是，在亚临床疾病的皮下接种大鼠中，大脑中可检测到病毒 RNA 以及 T 细胞浸润。本研究为 RVFV 脑炎的发病机制提供了新的见解。
