Secretory pathway antagonism by calicivirus homologues of Norwalk virus nonstructural protein p22 is restricted to noroviruses.
Secretory pathway antagonism by calicivirus homologues of Norwalk virus nonstructural protein p22 is restricted to noroviruses.
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DOI：
10.1186/1743-422x-9-181
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发表时间：
2012-09-03
期刊：
影响因子：
4.8
通讯作者：
Estes MK
中科院分区：
文献类型：
--
作者：
Sharp TM;Crawford SE;Ajami NJ;Neill FH;Atmar RL;Katayama K;Utama B;Estes MK
我们以前的报告，诺瓦克病毒非结构蛋白p22是一种细胞分泌途径的拮抗剂，这表明了一个新的方面诺如病毒/宿主相互作用。为了探索这种高度不同的杯状病毒蛋白的功能的保守性，我们研究了来自四种人类和两种小鼠诺如病毒和猫杯状病毒的p22同源物对分泌途径的影响。所有人类诺如病毒检查诱导高尔基体破坏和抑制蛋白质分泌，与基因组II.4休斯顿病毒是最有效的拮抗剂。基因组II.6病毒在模拟内质网输出信号（MERES）基序中具有保守突变，该基序在p22的人诺如病毒同源物中高度保守，并且对于分泌途径拮抗作用至关重要，并且这些病毒具有降低的高尔基体破坏和蛋白分泌抑制水平。p22同源物从持久性和非持久性株鼠诺如病毒诱导高尔基体破坏，但只有轻微抑制细胞蛋白分泌。猫杯状病毒p30不诱导高尔基体破坏或抑制细胞蛋白分泌。这些差异证实了诺如病毒对宿主细胞分泌途径拮抗作用的p22同源物，这可能会影响病毒复制和/或细胞发病机制。
Our previous report that the Norwalk virus nonstructural protein p22 is an antagonist of the cellular secretory pathway suggests a new aspect of norovirus/host interaction. To explore conservation of function of this highly divergent calicivirus protein, we examined the effects of p22 homologues from four human and two murine noroviruses, and feline calicivirus on the secretory pathway. All human noroviruses examined induced Golgi disruption and inhibited protein secretion, with the genogroup II.4 Houston virus being the most potent antagonist. Genogroup II.6 viruses have a conserved mutation in the mimic of an Endoplasmic Reticulum export signal (MERES) motif that is highly conserved in human norovirus homologues of p22 and is critical for secretory pathway antagonism, and these viruses had reduced levels of Golgi disruption and inhibition of protein secretion. p22 homologues from both persistent and nonpersistent strains of murine norovirus induced Golgi disruption, but only mildly inhibited cellular protein secretion. Feline calicivirus p30 did not induce Golgi disruption or inhibit cellular protein secretion. These differences confirm a norovirus-specific effect on host cell secretory pathway antagonism by homologues of p22, which may affect viral replication and/or cellular pathogenesis.