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 in vitro and higher pathogenicity in vivo compared with IBV strain B/Anhui-Baohe/127/2015 (AH127/15), only three amino acids differences (HA_A390E, NA_N342D and PB1_V212I) 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_A390E had a similar phenotype, whereas the recombinant virus harbouring PB1_V212I replicated to a moderately higher titre in both MDCK cells and in mice. Notably, the virus harbouring NA_N342D showed significantly better growth properties in MDCK cells and higher fatality rates in mice. In addition, the presence of NA_N342D dramatically enhanced the viral neuraminidase activity. In conclusion, our study identified a novel IBV molecular marker, NA_N342D, that could significantly increase the virulence of IBV in mice.

摘要

乙型流感病毒（IBV）是人类最重要的呼吸道病毒之一：每年引起全球约三分之一的与流感相关的疾病负担。但是，与已确定的甲型流感病毒（IAV）的几种致病性相关分子标记相比，对潜在的IBV致病性相关标记知之甚少。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，在体外具有更有效的复制能力，在体内具有更高的致病性），只有三个氨基酸差异（HA _A390E，NA _N342D和PB1 _V212I）在其完整基因组中被观察到。进一步研究了每种氨基酸差异对病毒致病性的贡献。与野生型IBV病毒rAH127相比，带有HA _A390E的单取代的重组病毒具有相似的表型，而_带有PB1 _V212I的重组病毒在MDCK细胞和小鼠中的滴度均较高。值得注意的是，_带有NA _N342D的病毒在MDCK细胞中表现出明显更好的生长特性，在小鼠中具有更高的死亡率。另外，NA _N342D的存在显着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NA _N342D，这可能会大大增加小鼠IBV的毒力。