Induction of intracellular membrane rearrangements by HAV proteins 2C and 2BC.
Induction of intracellular membrane rearrangements by HAV proteins 2C and 2BC.
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DOI：
10.1006/viro.1997.8775
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发表时间：
1997-10
期刊：
影响因子：
3.7
通讯作者：
N. Teterina;K. Bienz;D. Egger;A. Gorbalenya;E. Ehrenfeld
中科院分区：
文献类型：
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作者：
N. Teterina;K. Bienz;D. Egger;A. Gorbalenya;E. Ehrenfeld
甲型肝炎病毒（HAV）与其他小核糖核酸病毒的区别在于其在哺乳动物细胞培养物中缓慢且相对较差的非细胞病变性生长。HAV的2C和2BC蛋白与培养细胞中病毒生长的测定有关。来自其他小核糖核酸病毒（如脊髓灰质炎病毒）的同源蛋白已被证明具有多种活性，如RNA结合、核苷酸结合和NTR，以及膜结合和重组。这些活性中至少有一些是病毒RNA复制所必需的。我们在这里报告，甲型肝炎病毒2C和2BC蛋白，像他们的脊髓灰质炎病毒对应物，可以诱导细胞内膜的重排，并直接或间接地与膜相互作用。因此，HAV的低效复制特性不是2C（2BC）与膜相互作用的固有能力的结果。将来自HAV的细胞培养适应（cc）株的2C（2BC）蛋白序列的效果与来自HAV的野生型（wt）株或更快复制的致细胞病变（cp）株的相应蛋白序列的效果进行比较。分析表明，野生型病毒在适应细胞培养期间获得的突变不会显著改变这些蛋白质与膜结合并诱导膜改变的能力或诱导的膜结构的特定结构。另一方面，2C，而不是2BC，蛋白质从甲型肝炎病毒的cp株诱导不同的膜结构。
Hepatitis A virus (HAV) is distinguished from other picornaviruses by its slow and relatively poor, noncytopathic growth in cultures of mammalian cells. The 2C and 2BC proteins of HAV have been implicated in the determination of virus growth in cultured cells. The homologous proteins from other picornaviruses, such as poliovirus, have been demonstrated to exhibit multiple activities, such as RNA binding, nucleotide binding and NTPase, and membrane binding and reorganization. At least some of these activities are required for viral RNA replication. We report here that HAV 2C and 2BC proteins, like their poliovirus counterparts, can induce rearrangement of intracellular membranes and directly or indirectly interact with membranes. Therefore, the inefficient replication properties of HAV are not consequences of the inherent ability of 2C (2BC) to interact with membranes. The effect of 2C (2BC) protein sequences derived from a cell culture-adapted (cc) strain of HAV was compared with that of corresponding protein sequences from either a wild-type (wt) strain of HAV or a faster replicating cytopathic (cp) strain. The analysis demonstrated that mutations acquired in wt virus during adaptation to cell culture do not change dramatically either the ability of these proteins to associate with membranes and induce membrane alterations or the specific architecture of the induced membrane structures. On the other hand, 2C, but not 2BC, protein from the cp strain of HAV induced different membrane structures.