Collaboration of antibody and inflammation in clearance of rabies virus from the central nervous system
Collaboration of antibody and inflammation in clearance of rabies virus from the central nervous system
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DOI：
10.1128/jvi.72.5.3711-3719.1998
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发表时间：
1998-05-01
影响因子：
5.4
通讯作者：
Dietzschold, B
中科院分区：
文献类型：
--
作者：
Hooper, DC;Morimoto, K;Dietzschold, B
为了探讨细胞和体液免疫的不同方面在狂犬病病毒从中枢神经系统(CNS)清除中的作用，我们研究了缺乏B和T细胞、CD8(+)细胞毒性T细胞、B细胞、α/β干扰素(干扰素-α/β)受体、干扰素-γ受体或补体成分C3和C4的基因敲除小鼠的临床体征和病毒从中枢神经系统的清除。狂犬病减毒病毒CVS-F3鼻腔感染后，不同遗传背景的正常成年小鼠出现一过性疾病，表现为体重减轻和食欲下降，在感染后13天达到高峰。虽然这些动物在第21天P.I.完全康复，但缺乏B和T细胞或单独缺乏B细胞的小鼠发展为进行性疾病并死于感染。缺乏CD8(+)T细胞、干扰素受体或补体成分C3和C4的小鼠与具有相同遗传背景的完整小鼠相比，在临床体征的发展方面没有显著差异。然而，虽然在正常对照组小鼠中直到第8天P.I.才能检测到传染性病毒和病毒RNA，但在所有研究的基因敲除小鼠中，除C3和C4缺失的小鼠外，病毒感染一直持续到第21天。对狂犬病病毒特异性抗体产生的分析以及对感染动物脑部炎症的组织学评估表明，21天P.I.与感染早期(第8天P.I.)和快速(第10天P.I.)中枢神经系统的强烈炎症反应有关。随着大量病毒中和抗体(VNA)的产生，这些研究证实狂犬病VNA是清除已确定的狂犬病病毒感染的绝对要求。然而，要使后者及时发生，VNA和炎症机制之间的合作是必要的。
To investigate the involvement of various cellular and humoral aspects of immunity in the clearance of rabies virus from the central nervous system, (CNS), we studied the development of clinical signs and virus clearance from the CNS in knockout mice lacking either B and T cells, CD8(+) cytotoxic T cells, B cells, alpha/beta interferon (IFN-alpha/beta) receptors, IFN-gamma receptors, or complement components C3 and C4. Following intranasal infection with the attenuated rabies virus CVS-F3, normal adult mice of different genetic backgrounds developed a transient disease characterized by loss of body weight and appetite depression which peaked at 13 days post-infection (p.i.). While these animals had completely recovered by day 21 p.i., mice lacking either B and T cells or B cells alone developed a progressive disease and succumbed to infection. Mice lacking either CD8(+) T cells, IFN receptors, or complement components C3 and C4 showed no, significant differences in the development of clinical signs by comparison with intact counterparts having the same genetic background. However, while infectious virus and viral RNA could be detected in normal control mice only until day 8 p.i., in all of the gene knockout mice studied except those lacking C3 and C4, virus infection persisted through day 21 p.i. Analysis of rabies virus-specific antibody production together with histological assessment of brain inflammation in infected animals revealed that clearance of CVS-F3 by 21 days p.i. correlated with both a strong inflammatory response in the CNS early in the infection (day 8 p.i.), and the rapid (day 10 p.i.) production of significant levels of virus-neutralizing antibody (VNA), These studies confirm that rabies VNA is an absolute requirement for clearance of an established rabies virus infection. However, for the latter to occur in a timely fashion, collaboration between VNA and inflammatory mechanisms is necessary.