Amino acids at positions 273 and 394 in rabies virus nucleoprotein are important for both evasion of host RIG-I-mediated antiviral response and pathogenicity
Amino acids at positions 273 and 394 in rabies virus nucleoprotein are important for both evasion of host RIG-I-mediated antiviral response and pathogenicity
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DOI：
10.1016/j.virusres.2010.09.016
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发表时间：
2011-01-01
期刊：
影响因子：
5
通讯作者：
Sugiyama, Makoto
中科院分区：
文献类型：
--
作者：
Masatani, Tatsunori;Ito, Naoto;Sugiyama, Makoto
我们以前报道过核蛋白（N）与强毒株西原（Ni）和弱毒株Ni-CE的不同致病性有关，并且Ni N而不是Ni-CE N具有逃避视黄酸诱导基因I（RIG-I）介导的先天免疫的功能。Ni和Ni-CE N之间存在三个氨基酸差异（在位置273、394和395处），表明这些突变之一或突变的组合对于先天免疫的致病性和逃避是重要的。我们产生了Ni-CE突变体，其中Ni-CE N中的氨基酸在所有组合中都被Ni的氨基酸取代。在这些突变体中，在位置273和394处具有突变的CE（NiN 273/394）最有效地逃避RIG-I介导的信号传导的激活，并且也显示出最高的致病性。这种相关性加强了逃避宿主RIG-I介导的先天免疫与狂犬病病毒致病性之间的关系。(C)2010爱思唯尔有限公司版权所有。
We previously reported that nucleoprotein (N) is related to the different pathogenicities of the virulent rabies virus strain Nishigahara (Ni) and avirulent strain Ni-CE and also that Ni N, but not Ni-CE N, functions to evade retinoic acid-inducible gene I (RIG-I)-mediated innate immunity. There are three amino acid differences between Ni and Ni-CE N (at positions 273, 394 and 395), indicating that one of these mutations or a combination of mutations is important for the pathogenicity and evasion of innate immunity. We generated Ni-CE mutants in which the amino acids in Ni-CE N were replaced with those of Ni in all combinations. Among the mutants, CE(NiN273/394) with mutations at positions 273 and 394 evaded activation of RIG-I-mediated signaling most efficiently and also showed the highest pathogenicity. This correlation reinforces the relation between evasion of host RIG-I-mediated innate immunity and pathogenicity of rabies virus. (C) 2010 Elsevier B.V. All rights reserved.