hsp72, a host determinant of measles virus neurovirulence
hsp72, a host determinant of measles virus neurovirulence
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DOI：
10.1128/jvi.01438-06
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发表时间：
2006-11-01
影响因子：
5.4
通讯作者：
Oglesbee, Michael
中科院分区：
文献类型：
--
作者：
Carsillo, Thomas;Traylor, Zachary;Oglesbee, Michael
短暂的高热，如在发热事件中经历的增加主要诱导70 kDa热休克蛋白（HSP 72）的表达。尽管发热事件的相关性病毒的发病机制和热休克蛋白在病毒复制和基因表达的多种体外作用，在体内的意义病毒热休克蛋白的相互作用是未知的。本研究利用麻疹病毒（MV）脑炎小鼠模型，确定了hsp 72水平与hsp 72应答病毒的神经毒力之间的体内关系。转基因C57 BL/6小鼠被创建为在神经元中组成型过表达hsp 72，并且这些小鼠在42小时龄时颅内接种Edmonston MV（艾德MV）。感染后2 - 4周，转基因动物脑中的平均病毒RNA负荷比非转基因动物高约2个数量级，这种增加的负荷与死亡率增加5倍相关。还用表现出对病毒转录的hsp 72依赖性刺激的体外应答减弱的艾德W变体（艾德N-522 D）攻击小鼠。该病毒在转基因小鼠中表现出减弱的神经致病性，其中死亡率和病毒RNA负荷与感染艾德N-522 D或亲本艾德W的非转基因小鼠没有显著差异。总的来说，这些结果表明，热休克蛋白72水平可以作为一个主机的决定因素的病毒神经毒力在C57 BL/6小鼠，反映了直接影响热休克蛋白72对病毒基因表达。
Transient hyperthermia such as that experienced during febrile episodes increases expression of the major inducible 70-kDa heat shock protein (hsp72). Despite the relevance of febrile episodes to viral pathogenesis and the multiple in vitro roles of heat shock proteins in viral replication and gene expression, the in vivo significance of virus-heat shock protein interactions is unknown. The present work determined the in vivo relationship between hsp72 levels and neurovirulence of an hsp72-responsive virus using the mouse model of measles virus (MV) encephalitis. Transgenic C57BL/6 mice were created to constitutively overexpress hsp72 in neurons, and these mice were inoculated intracranially with Edmonston MV (Ed MV) at 42 h of age. The mean viral RNA burden in brain was approximately 2 orders of magnitude higher in transgenic animals than in nontransgenic animals 2 to 4 weeks postinfection, and this increased burden was associated with a fivefold increase in mortality. Mice were also challenged with an Ed W variant exhibiting an attenuated in vitro response to hsp72-dependent stimulation of viral transcription (Ed N-522D). This virus exhibited an attenuated neuropathogenicity in transgenic mice, where mortality and viral RNA burdens were not significantly different from nontransgenic mice infected with either Ed N-522D or parent Ed W. Collectively, these results indicate that hsp72 levels can serve as a host determinant of viral neurovirulence in C57BL/6 mice, reflecting the direct influence of hsp72 on viral gene expression.