A Point Mutation in the Human Parainfluenza Virus Type 2 Nucleoprotein Leads to Two Separate Effects on Virus Replication
A Point Mutation in the Human Parainfluenza Virus Type 2 Nucleoprotein Leads to Two Separate Effects on Virus Replication
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人类副流感病毒 2 型核蛋白的点突变对病毒复制产生两种不同的影响
DOI：
10.1128/jvi.02067-21
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发表时间：
2022
影响因子：
5.4
通讯作者：
Nishio Machiko
中科院分区：
文献类型：
--
作者：
Saka Naoki;Matsumoto Yusuke;Ohta Keisuke;Kolakofsky Daniel;Nishio Machiko
副粘病毒基因组，如人类副流感病毒2型（hPIV 2），具有精确的六个核苷酸的倍数（“六规则”）的长度，其中每个核蛋白亚基（NP）恰好结合六个核苷酸。它的RNA结合沟的10个残基接触基因组RNA;但只有一个，Q202，直接接触核苷酸碱基。NPQ 202的突变导致两种表型：病毒聚合酶复制具有缺陷型二分启动子（NPW失活）的微型基因组的能力，以及无法通过标准方法拯救携带该点突变的rPIV 2。rPIV 2 NPQ 202 A的缺失阻止了对后者表型的进一步研究。通过转染细胞的广泛和重复共培养，最终回收了携带该突变的rPIV 2，由于存在额外的NP突变（I35 L），该病毒显然是活的。我们的研究结果表明，这两种表型是由于Q202突变的单独影响，重要提示副粘病毒基因组包含在其核蛋白（NP）的非共价均聚物中，并形成螺旋状核衣壳（NC）其3′端含有启动病毒RNA合成的启动子。这项工作表明，这些NC 3′末端可能通过与病毒修饰的细胞膜的特异性相互作用在病毒生命周期中发挥另一种作用，这些细胞膜是将病毒NC掺入出芽病毒体所必需的。
Paramyxovirus genomes, like that of human parainfluenza virus type 2 (hPIV2), have lengths of precisely multiples-of-six nucleotides (“rule of six”), where each nucleoprotein subunit (NP) binds exactly six nucleotides. Ten residues of its RNA binding groove contact the genome RNA; but only one, Q202, directly contacts a nucleotide base. The mutation of NPQ202leads to two phenotypes: the ability of the viral polymerase to replicate minigenomes with defective bipartite promoters where NPwtis inactive, and the inability to rescue rPIV2 carrying this point mutation by standard means. The absence of an rPIV2 NPQ202Aprevented further study of the latter phenotype. By extensive and repeated cocultivation of transfected cells, an rPIV2 carrying this mutation was finally recovered, and this virus was apparently viable due to the presence of an additional NP mutation (I35L). Our results suggest that these two phenotypes are due to separate effects of the Q202 mutation, and that the problematic rescue phenotype may be due to the inability of the transfected cell to incorporate viral nucleocapsids during virus budding.IMPORTANCEParamyxovirus genomes are contained within a noncovalent homopolymer of its nucleoprotein (NP) and form helical nucleocapsids (NC) whose 3′ ends contain the promoters for the initiation of viral RNA synthesis. This work suggests that these NC 3′ ends may play another role in the virus life cycle via their specific interaction with virus-modified cell membranes needed for the incorporation of viral NCs into budding virions.
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影响因子：
5.4
作者：
Raux, Helene;Obiang, Linda;Gaudin, Yves
通讯作者：
Gaudin, Yves
影响因子：
3.7
作者：
M. Nishio;M. Tsurudome;H. Ishihara;Morihiro Ito;Yasuhiko Ito
通讯作者：
M. Nishio;M. Tsurudome;H. Ishihara;Morihiro Ito;Yasuhiko Ito
人副流感病毒2型V蛋白通过与L蛋白结合抑制基因组复制；
DOI：
--
发表时间：
2008
期刊：
J Virol (Epub ahead of print)
影响因子：
--
作者：
Nishio;M. Ohtsuka;J. Tsurudome;M. Nosaka;T. Kolakofsky;D
通讯作者：
D
影响因子：
3.8
作者：
Nishio, M;Tsurudome, M;Ito, Y
通讯作者：
Ito, Y
2 型人类副流感病毒形成丝状颗粒。
DOI：
10.1099/0022-1317-81-5-1305
发表时间：
2000
期刊：
The Journal of general virology.
影响因子：
--
作者：
Yao,Q;Compans,RW
通讯作者：
Compans,RW