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流感 A 病毒 RNA 聚合酶的人工杂种揭示 PA 亚基调节其热敏感性。

Artificial hybrids of influenza A virus RNA polymerase reveal PA subunit modulates its thermal sensitivity.

机构信息

Division of Infectious Disease, Department of Infectious Medicine, Kurume University School of Medicine, Kurume, Japan.

出版信息

PLoS One. 2010 Dec 7;5(12):e15140. doi: 10.1371/journal.pone.0015140.

DOI:10.1371/journal.pone.0015140
PMID:21151876
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2998429/
Abstract

BACKGROUND

Influenza A virus can infect a variety of different hosts and therefore has to adapt to different host temperatures for its efficient viral replication. Influenza virus codes for an RNA polymerase of 3 subunits: PB1, PB2 and PA. It is well known that the PB2 subunit is involved in temperature sensitivity, such as cold adaptation. On the other hand the role of the PA subunit in thermal sensitivity is still poorly understood.

METHODOLOGY/PRINCIPAL FINDINGS: To test which polymerase subunit(s) were involved in thermal stress we reconstituted artificial hybrids of influenza RNA polymerase in ribonucleoprotein (RNP) complexes and measured steady-state levels of mRNA, cRNA and vRNA at different temperatures. The PA subunit was involved in modulating RNP activity under thermal stress. Residue 114 of the PA subunit was an important determinant of this activity.

CONCLUSIONS/SIGNIFICANCE: These findings suggested that influenza A virus may acquire an RNA polymerase adapted to different body temperatures of the host by reassortment of the RNA polymerase genes.

摘要

背景

甲型流感病毒可以感染多种不同的宿主,因此必须适应不同宿主的温度以实现其有效的病毒复制。流感病毒的 RNA 聚合酶由 3 个亚基组成:PB1、PB2 和 PA。众所周知,PB2 亚基参与温度敏感性,例如冷适应。另一方面,PA 亚基在热敏感性中的作用仍知之甚少。

方法/主要发现:为了测试聚合酶亚基(s)在热应激中参与的情况,我们在核糖核蛋白(RNP)复合物中重新构建了流感 RNA 聚合酶的人工杂种,并在不同温度下测量 mRNA、cRNA 和 vRNA 的稳态水平。PA 亚基参与调节热应激下的 RNP 活性。PA 亚基的 114 位残基是该活性的重要决定因素。

结论/意义:这些发现表明,甲型流感病毒可能通过 RNA 聚合酶基因的重排获得适应宿主不同体温的 RNA 聚合酶。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/80e04e9124b8/pone.0015140.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/4b4a7a8aeb16/pone.0015140.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/c8e8e27769ea/pone.0015140.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/403d0879c2b1/pone.0015140.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/e7b7f13156b7/pone.0015140.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/89d09a80249c/pone.0015140.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/80e04e9124b8/pone.0015140.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/4b4a7a8aeb16/pone.0015140.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/c8e8e27769ea/pone.0015140.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/403d0879c2b1/pone.0015140.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/e7b7f13156b7/pone.0015140.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/89d09a80249c/pone.0015140.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c03/2998429/80e04e9124b8/pone.0015140.g006.jpg

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