Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses
Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses
复制标题
DOI：
10.1128/jvi.75.11.5398-5404.2001
复制
发表时间：
2001-06-01
影响因子：
5.4
通讯作者：
Naffakh, N
中科院分区：
文献类型：
--
作者：
Massin, P;van der Werf, S;Naffakh, N
人类甲型流感病毒在上呼吸道的复制温度约为33摄氏度，而禽流感病毒在肠道的复制温度接近41摄氏度。在本研究中，我们分析了低温（33 ℃）对培养细胞中禽流感病毒和人流感病毒RNA复制的影响。人A/Puerto-Rico/8/34和A/Sydney/5/97病毒在33 ℃和37 ℃时NP片段的复制动力学相似，而禽A/FPV/罗斯托克/ 34和A/野鸭/NY/6750/78病毒在33 ℃时的复制比37 ℃时延迟。利用一个用于功能性核糖核蛋白体内重组的遗传系统，我们观察到来源于禽病毒而非人病毒的聚合酶复合物在哺乳动物细胞中表现出冷敏感性，这主要取决于PB 2的残基627，我们的研究结果表明，禽流感病毒聚合酶复合体在33 ℃下确保病毒基因组复制的能力降低，导致它们无法在人体内有效生长。
Human influenza A viruses replicate in the upper respiratory tract at a temperature of about 33 degreesC, whereas avian viruses replicate in the intestinal tract at a temperature close to 41 degreesC. In the present study, we analyzed the influence of low temperature (33 degreesC) on RNA replication of avian and human viruses in cultured cells. The kinetics of replication of the NP segment were similar at 33 and 37 degreesC for the human A/Puerto-Rico/8/34 and A/Sydney/5/97 viruses, whereas replication was delayed at 33 degreesC compared to 37 degreesC for the avian A/FPV/Rostock/ 34 and A/Mallard/NY/6750/78 viruses. Making use of a genetic system for the in vivo reconstitution of functional ribonucleoproteins, we observed that the polymerase complexes derived from avian viruses but not human viruses exhibited cold sensitivity in mammalian cells, which was determined mostly by residue 627 of PB2, Our results suggest that a reduced ability of the polymerase complex of avian viruses to ensure replication of the viral genome at 33 degreesC could contribute to their inability to grow efficiently in humans.