Immune evasion by rabies viruses through the maintenance of blood-brain barrier integrity
Immune evasion by rabies viruses through the maintenance of blood-brain barrier integrity
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DOI：
10.1080/13550280802235924
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发表时间：
2008-01-01
影响因子：
3.2
通讯作者：
Hooper, D. Craig
中科院分区：
文献类型：
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作者：
Roy, Anirban;Hooper, D. Craig
如果效应器能够穿过血脑屏障（BBB），则减毒狂犬病病毒（RV）毒株挑战病毒标准（CVS）-F3和与银毛蝙蝠（SHBRV）相关的高致病性毒株都可以通过适当的抗病毒免疫机制从中枢神经系统（CNS）组织中清除。在 SHBRV 感染的情况下，抗病毒免疫在外周正常发展，但无法打开血脑屏障，通常会导致致命的结果。为了确定 CNS 靶向免疫反应的缺失是否与其他致病性 RV 毒株的感染有关，我们评估了感染多种 RV 毒株（包括导致大多数人类狂犬病病例的狗变种）的小鼠的免疫发展、BBB 通透性和免疫细胞对 CNS 组织的浸润。我们证明，感染多种已知致病性 RV 菌株的致命结果确实与无法跨 BBB 传递免疫效应物有关。易患中枢神经系统炎症的小鼠感染某些病毒后的存活率得到提高。结果表明，到达中枢神经系统组织的免疫效应物的活性与病毒固有的病理属性之间的竞争决定了结果，将 RV 特异性免疫效应物传递到中枢神经系统组织的干预措施可能对狂犬病具有普遍的治疗价值。
The attenuated rabies virus (RV) strain Challenge Virus Standard (CVS)-F3 and a highly pathogenic strain associated with the silver-haired bats (SHBRV) can both be cleared from the central nervous system (CNS) tissues by appropriate antiviral immune mechanisms if the effectors are provided access across the blood-brain barrier (BBB). In the case of SHBRV infection, antiviral immunity develops normally in the periphery but fails to open the BBB, generally resulting in a lethal outcome. To determine whether or not an absence in the CNS targeted immune response is associated with the infection with other pathogenic RV strains, we have assessed the development of immunity, BBB permeability, and immune cell infiltration into the CNS tissues of mice infected with a variety of RV strains, including the dog variants responsible for the majority of human rabies cases. We demonstrate that the lethal outcomes of infection with a variety of known pathogenic RV strains are indeed associated with the inability to deliver immune effectors across the BBB. Survival from infection with certain of these viruses is improved in mice prone to CNS inflammation. The results suggest that competition between the activity of the immune effectors reaching CNS tissues and the inherent pathological attributes of the virus dictates the outcome and that intervention to deliver RV-specific immune effectors into CNS tissues may have general therapeutic value in rabies.