Zhirnov O P, Syrtsev V V, Schwalm F, Klenk H D
Vopr Virusol. 2011 Jul-Aug;56(4):14-8.
The authors studied a possible role of the caspase cleavage motif located in the nucleoprotein (NP) of pandemic influenza virus H1N1 in the regulation of viral virulence properties. A reverse genetics method was used to obtain chimeric seasonal-like mouse-adapted influenza virus hvA/PE/8/34 (H1N10) carrying either the NP gene of wild type pandemic virus with incomplete caspase motif ETGC or mutated pandemic NP with natural caspase cleavage site of human type ETDG. The wild-type NP gene of the pandemic virus was found to poorly fit to the gene pattern of closely related seasonal-like hvA/PR/8/34 virus (H1N1) and did not rescue mature virus production whereas a mutated NP with human-type caspase cleavage site maintained gene fitness, giving rise to a chimeric virus. The generated chimeric virus hvA/PR/8/34 carrying the mutated pandemic NP successfully replicated in the murine lung, but was attenuated and did not reach the virulence level of seasonal-like mouse-adapted virus hvA/PR/8/34. The findings indicate that the NP caspase cleavage site plays a role in viral adaptation and viral virulence in mammals.
作者研究了甲型H1N1大流行性流感病毒核蛋白（NP）中的半胱天冬酶切割基序在调节病毒毒力特性中的可能作用。采用反向遗传学方法获得嵌合的季节性样小鼠适应型流感病毒hvA/PE/8/34（H1N10），其携带具有不完全半胱天冬酶基序ETGC的野生型大流行病毒NP基因或具有人源型ETDG天然半胱天冬酶切割位点的突变大流行NP基因。发现大流行病毒的野生型NP基因与密切相关的季节性样hvA/PR/8/34病毒（H1N1）的基因模式不太匹配，无法拯救成熟病毒的产生，而具有人源型半胱天冬酶切割位点的突变NP维持了基因适应性，产生了嵌合病毒。携带突变大流行NP的嵌合病毒hvA/PR/8/34在小鼠肺中成功复制，但毒力减弱，未达到季节性样小鼠适应型病毒hvA/PR/8/34的毒力水平。这些发现表明，NP半胱天冬酶切割位点在哺乳动物的病毒适应性和病毒毒力中起作用。
