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Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains

机译：毒性和减毒的痘苗病毒株感染小鼠中枢神经系统后的差异反应。

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Viral infections of the central nervous system (CNS) lead to a broad range of pathologies. CNS infections with Orthopox viruses have been mainly documented as an adverse reaction to smallpox vaccination with vaccinia virus. To date, there is insufficient data regarding the mechanisms underlying pathological viral replication or viral clearance. Therefore, informed risk assessment of vaccine adverse reactions or outcome prediction is limited. This work applied a model of viral infection of the CNS, comparing neurovirulent with attenuated strains. We followed various parameters along the disease and correlated viral load, morbidity, and mortality with tissue integrity, innate and adaptive immune response and functionality of the blood–brain barrier. Combining these data with whole brain RNA-seq analysis performed at different time points indicated that neurovirulence is associated with host immune silencing followed by induction of tissue damage-specific pathways. In contrast, brain infection with attenuated strains resulted in rapid and robust induction of innate and adaptive protective immunity, followed by viral clearance and recovery. This study significantly improves our understanding of the mechanisms and processes determining the consequence of viral CNS infection and highlights potential biomarkers associated with such outcomes.
机译：中枢神经系统（CNS）的病毒感染导致多种病理。正痘病毒感染中枢神经系统感染主要被证明是对痘苗病毒天花疫苗的不良反应。迄今为止，关于病理性病毒复制或病毒清除的机制尚无足够的数据。因此，疫苗不良反应或结果预测的知情风险评估是有限的。这项工作应用了CNS病毒感染的模型，将神经毒力与减毒株进行了比较。我们跟踪疾病的各种参数，并将病毒载量，发病率和死亡率与组织完整性，先天性和适应性免疫反应以及血脑屏障功能相关。将这些数据与在不同时间点进行的全脑RNA序列分析相结合，表明神经毒力与宿主免疫沉默相关，随后诱导组织损伤特异性途径。相反，减毒株的脑部感染导致先天性和适应性保护性免疫的快速而强大的诱导，随后是病毒的清除和恢复。这项研究显着提高了我们对决定病毒中枢神经系统感染后果的机制和过程的理解，并强调了与此类结果相关的潜在生物标志物。

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