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乙型流感病毒 NA 蛋白中的单个 N342D 取代决定了病毒在小鼠中的致病性。

A single N342D substitution in Influenza B Virus NA protein determines viral pathogenicity in mice.

机构信息

School of Public Health (Shenzhen), Sun Yat-sen University, Guangdong, People's Republic of China.

National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.

出版信息

Emerg Microbes Infect. 2020 Dec;9(1):1853-1863. doi: 10.1080/22221751.2020.1806005.

DOI:10.1080/22221751.2020.1806005
PMID:32746754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7473139/
Abstract

Influenza B virus (IBV) is one of the most important human respiratory viruses: it causes approximately one-third of the global influenza-related disease burden each year. However, compared with the several pathogenicity-related molecular markers that have been identified for influenza A virus (IAV), little is known about potential IBV pathogenicity-related markers. Here, although the IBV strain B/Anhui-Tunxi/1528/2014 (AH1528/14) exhibited a more efficient replication ability and higher pathogenicity compared with IBV strain B/Anhui-Baohe/127/2015 (AH127/15), only three amino acids differences (HA, NA and PB1) were observed among their full genomes. The contributions of each amino acid difference to the virus pathogenicity were further investigated. Compared with the wild type IBV virus rAH127, the recombinant virus harbouring a single substitution of HA had a similar phenotype, whereas the recombinant virus harbouring PB1 replicated to a moderately higher titre in both MDCK cells and in mice. Notably, the virus harbouring NA showed significantly better growth properties in MDCK cells and higher fatality rates in mice. In addition, the presence of NA dramatically enhanced the viral neuraminidase activity. In conclusion, our study identified a novel IBV molecular marker, NA, that could significantly increase the virulence of IBV in mice.

摘要

乙型流感病毒（IBV）是最重要的人类呼吸道病毒之一：它每年导致约全球三分之一的流感相关疾病负担。然而，与已确定的几种与致病性相关的甲型流感病毒（IAV）分子标记物相比，人们对潜在的 IBV 致病性相关标记物知之甚少。在这里，尽管 IBV 株 B/Anhui-Tunxi/1528/2014（AH1528/14）与 IBV 株 B/Anhui-Baohe/127/2015（AH127/15）相比表现出更高的复制能力和更强的致病性，但在它们的全基因组中仅观察到三个氨基酸差异（HA、NA 和 PB1）。进一步研究了每个氨基酸差异对病毒致病性的贡献。与野生型 IBV 病毒 rAH127 相比，携带 HA 单一取代的重组病毒表现出相似的表型，而携带 PB1 的重组病毒在 MDCK 细胞和小鼠中复制到中等较高的滴度。值得注意的是，携带 NA 的病毒在 MDCK 细胞中的生长特性明显更好，在小鼠中的死亡率更高。此外，NA 的存在极大地增强了病毒神经氨酸酶活性。总之，我们的研究确定了一种新型的 IBV 分子标记物 NA，它可以显著增加 IBV 在小鼠中的毒力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/1aae46c5b4f9/TEMI_A_1806005_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/19e8c427ea78/TEMI_A_1806005_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/62171c7cf6f5/TEMI_A_1806005_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/a92b8cf95501/TEMI_A_1806005_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/6cdf7d62af5b/TEMI_A_1806005_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/cf7c22f9c789/TEMI_A_1806005_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/3915d1d174b3/TEMI_A_1806005_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/1aae46c5b4f9/TEMI_A_1806005_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/19e8c427ea78/TEMI_A_1806005_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/62171c7cf6f5/TEMI_A_1806005_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/a92b8cf95501/TEMI_A_1806005_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/6cdf7d62af5b/TEMI_A_1806005_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/cf7c22f9c789/TEMI_A_1806005_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/3915d1d174b3/TEMI_A_1806005_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f7/7473139/1aae46c5b4f9/TEMI_A_1806005_F0007_OC.jpg

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