B型流感病毒B/Guangxi-Jiangzhou/1352/2018毒株的遗传进化及其对小鼠的致病性分析

Phylogenetic and pathogenicity analysis of influenza B virus strain B/Guangxi-Jiangzhou/1352/2018

摘要:

B型流感病毒(influenza B virus,IBV)比A型流感病毒(influenza A virus,IAV)更易引发并发症，在一定季节内造成的疾病负担甚至超过IAV，但目前人们对IBV的关注较少。为了分析IBV临床毒株B/Guangxi-Jiangzhou/1352/2018的遗传进化特点，本研究构建了系统进化树，并以世界卫生组织推荐的疫苗株为参考，对其血凝素(hemagglutinin,HA)和神经氨酸酶(neuraminidase,NA)进行了氨基酸序列同源性及突变位点分析。分析结果发现B/Guangxi-Jiangzhou/1352/2018毒株无谱系间重配现象，与同年疫苗株B/Colorado/06/2017匹配性较差。另外，测定了B/Guangxi-Jiangzhou/1352/2018毒株感染小鼠的半数致死量(median lethal dose,LD₅₀)及其对小鼠的致病性。结果表明，B/Guangxi-Jiangzhou/1352/2018毒株感染小鼠的LD₅₀为10^5.9TCID₅₀(median tissue culture infective dose)，小鼠肺脏中病毒滴度在感染后1 d达到高峰，炎性细胞因子的mRNA水平在感染后12 h达到高峰，且感染后肺脏中的肺泡损伤严重，有大量炎性细胞浸润。本研究证明了IBV临床毒株B/Guangxi-Jiangzhou/1352/2018可以感染小鼠并诱发典型的肺脏炎症，为研究IBV致病及传播机制奠定了基础，为评价新型流感疫苗、抗病毒和抗炎症药物提供了理想的动物模型。

关键词:B型流感病毒;Victoria谱系;遗传进化分析;致病性;动物模型

Abstract:

Influenza B virus (IBV) is more likely to cause complications than influenza A virus (IAV) and even causes higher disease burden than IAV in a certain season, but IBV has received less attention. In order to analyze the genetic evolution characteristics of the clinical strain IBV (B/Guangxi- Jiangzhou/1352/2018), we constructed genetic evolution trees and analyzed the homology and different amino acids of hemagglutinin and neuraminidase referring to the vaccine strains recommended by World Health Organization (WHO). We found that strain B/Guangxi-Jiangzhou/1352/2018 was free of interlineage reassortment and poorly matched with the vaccine strain B/Colorado/06/2017 of the same year. We also determined the median lethal dose (LD₅₀) and the pathogenicity of strain B/Guangxi-Jiangzhou/1352/2018 in mice. The results showed that the LD₅₀was 10^5.9 TCID₅₀(median tissue culture infective dose), the IBV titer in the lungs reached peak 1 d post infection and the mRNA level of the most of inflammatory cytokines in the lungs reached peak 12 h post infection. The alveoli in the lungs were severely damaged and a large number of inflammatory cells were infiltrated post infection. The study demonstrated that the clinical strain IBV (B/Guangxi-Jiangzhou/1352/2018) could infect mice and induce typical lung inflammation. This will facilitate the research on the pathogenesis and transmission mechanism of IBV, and provide an ideal animal model for evaluation of new vaccines, antiviral and anti-inflammatory drug.

Key words:influenza B virus;Victoria lineage;genetic analysis;pathogenicity;animal model