Venezuelan equine encephalitis virus (VEEV) is a positively-stranded RNA arbovirus of the genus Alphavirus that causes encephalitis in humans. Cynomolgus macaques are a relevant model of the human disease caused by VEEV and are useful in exploring pathogenic mechanisms and the host response to VEEV infection. Macaques were exposed to small-particle aerosols containing virus derived from an infectious clone of VEEV strain INH-9813, a subtype IC strain isolated from a human infection. VEEV-exposed macaques developed a biphasic fever after infection similar to that seen in humans. Maximum temperature deviation correlated with the inhaled dose, but fever duration did not. Neurological signs, suggestive of virus penetration into the CNS, were predominantly seen in the second febrile period. Electroencephalography data indicated a statistically significant decrease in all power bands and circadian index during the second febrile period that returned to normal after fever resolved. Intracranial pressure increased late in the second febrile period. On day 6 post-infection macaques had high levels of MCP-1 and IP-10 chemokines in the CNS, as well as a marked increase of T lymphocytes and activated microglia. More than four weeks after infection, viral genomic RNA was found in the brain, cerebrospinal fluid and cervical lymph nodes. Pro-inflammatory cytokines & chemokines, infiltrating leukocytes and pathological changes were seen in the CNS tissues of macaques euthanized at these times. These data are consistent with persistence of virus replication and/or genomic RNA and potentially, inflammatory sequelae in the central nervous system after resolution of acute VEEV disease.

中文翻译：

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暴露于雾化委内瑞拉马脑炎病毒的猕猴中枢神经系统中病毒 RNA 和炎症的长期持续存在

委内瑞拉马脑炎病毒 (VEEV) 是甲病毒属的正链 RNA 虫媒病毒这会导致人类脑炎。食蟹猴是由 VEEV 引起的人类疾病的相关模型，可用于探索致病机制和宿主对 VEEV 感染的反应。猕猴暴露于含有病毒的小颗粒气溶胶中，该病毒源自 VEEV 毒株 INH-9813 的传染性克隆，这是一种从人类感染中分离出来的亚型 IC 毒株。暴露于 VEEV 的猕猴在感染后会出现与人类相似的双相热。最高温度偏差与吸入剂量相关，但发热持续时间没有。提示病毒侵入中枢神经系统的神经系统体征主要出现在第二次发热期。脑电图数据表明，在第二次发热期间，所有功率带和昼夜节律指数均出现统计学显着下降，发热消退后恢复正常。第二次发热后期颅内压升高。在感染后第 6 天，猕猴的中枢神经系统中具有高水平的 MCP-1 和 IP-10 趋化因子，以及 T 淋巴细胞和活化的小胶质细胞显着增加。感染 4 周多后，在大脑、脑脊液和颈部淋巴结中发现了病毒基因组 RNA。在这些时间安乐死的猕猴的中枢神经系统组织中观察到促炎细胞因子和趋化因子、浸润的白细胞和病理变化。这些数据与病毒复制和/或基因组 RNA 的持续性一致，并且可能，