Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130000, China.
Jilin Agricultural University, Changchun, 130118, China.
Virol J. 2021 Nov 22;18(1):230. doi: 10.1186/s12985-021-01703-z.
In 2011, a new influenza virus, named Influenza D Virus (IDV), was isolated from pigs, and then cattle, presenting influenza-like symptoms. IDV is one of the causative agents of Bovine Respiratory Disease (BRD), which causes high morbidity and mortality in feedlot cattle worldwide. To date, the molecular mechanisms of IDV pathogenicity are unknown. Recent IDV outbreaks in cattle, along with serological and genetic evidence of IDV infection in humans, have raised concerns regarding the zoonotic potential of this virus. Influenza virus polymerase is a determining factor of viral pathogenicity to mammals.
Here we take a prospective approach to this question by creating a random mutation library about PB2 subunit of the IDV viral polymerase to test which amino acid point mutations will increase viral polymerase activity, leading to increased pathogenicity of the virus.
Our work shows some exact sites that could affect polymerase activities in influenza D viruses. For example, two single-site mutations, PB2-D533S and PB2-G603Y, can independently increase polymerase activity. The PB2-D533S mutation alone can increase the polymerase activity by 9.92 times, while the PB2-G603Y mutation increments the activity by 8.22 times.
Taken together, our findings provide important insight into IDV replication fitness mediated by the PB2 protein, increasing our understanding of IDV replication and pathogenicity and facilitating future studies.
2011 年，一种新型流感病毒，即流感 D 病毒（IDV），从猪身上分离出来，随后在牛身上出现了类似流感的症状。IDV 是牛呼吸道疾病（BRD）的病原体之一，在全球范围内导致肥育牛的高发病率和死亡率。迄今为止，IDV 致病的分子机制尚不清楚。最近 IDV 在牛群中的爆发，以及 IDV 感染人类的血清学和遗传学证据，引起了人们对这种病毒人畜共患潜力的关注。流感病毒聚合酶是病毒对哺乳动物致病性的决定因素。
在这里，我们通过创建一个关于 IDV 病毒聚合酶 PB2 亚单位的随机突变文库来前瞻性地解决这个问题，以测试哪些氨基酸点突变将增加病毒聚合酶活性，从而导致病毒致病性增加。
我们的工作表明了一些确切的位点，这些位点可能会影响流感 D 病毒中的聚合酶活性。例如，两个单点突变 PB2-D533S 和 PB2-G603Y 可以独立地增加聚合酶活性。PB2-D533S 突变本身可以将聚合酶活性提高 9.92 倍，而 PB2-G603Y 突变则使活性提高 8.22 倍。
总之，我们的发现为 PB2 蛋白介导的 IDV 复制适应性提供了重要的见解，增加了我们对 IDV 复制和致病性的理解，并为未来的研究提供了便利。
