猪甲型流感病毒(swIAV)的特征在于高突变率和人畜共患和大流行的可能性。为了得出有关猪的毒力和对人类的致病性的结论,我们检查了分子标记和辅助蛋白的存在,与疫苗株的交叉反应,5株H1N1病毒对抗病毒药物的耐药性。
■在MEGA7.0软件和流感研究数据库中分析了五个先前遗传表征的swIAV的氨基酸(AA)序列。
■氨基酸分析显示三种病毒株在碱性聚合酶2(PB2)AA链内具有590S/591R多态性和T271A取代,导致哺乳动物细胞中病毒复制增强。另外两个菌株在PB2中具有D701N和R251K取代,并合成了PB1-F2蛋白,这是猪聚合酶活性和毒力增加的因素。所有菌株都合成了PB1-N40,PA-N155,PA-N182和PA-X蛋白,这些蛋白负责增强哺乳动物细胞中的复制并下调宿主的免疫反应。在血凝素抗原位点内检测到的突变意味着五种分析的病毒相对于疫苗株的抗原漂移。所有病毒对神经氨酸酶抑制剂和巴洛沙韦,这在人类偶然感染的情况下很重要。
■在所分析的病毒中检测到毒力标记和辅助蛋白表明它们在哺乳动物细胞中复制的倾向更高,毒力增加,以及传播给人类的可能性,并暗示流感疫苗的功效受损。
UNASSIGNED: Swine influenza A viruses (swIAVs) are characterised by high mutation rates and zoonotic and pandemic potential. In order to draw conclusions about virulence in swine and pathogenicity to humans, we examined the existence of molecular markers and accessory proteins, cross-reactivity with vaccine strains, and resistance to antiviral drugs in five strains of H1N1 swIAVs.
UNASSIGNED: Amino acid (AA) sequences of five previously genetically characterised swIAVs were analysed in MEGA 7.0 software and the Influenza Research Database.
UNASSIGNED: Amino acid analysis revealed three virus strains with 590S/591R polymorphism and T271A substitution within basic polymerase 2 (PB2) AA chains, which cause enhanced virus replication in mammalian cells. The other two strains possessed D701N and R251K substitutions within PB2 and synthesised PB1-F2 protein, which are the factors of increased polymerase activity and virulence in swine. All strains synthesised PB1-N40, PA-N155, PA-N182, and PA-X proteins responsible for enhanced replication in mammalian cells and downregulation of the immune response of the host. Mutations detected within haemagglutinin antigenic sites imply the antigenic drift of the five analysed viruses in relation to the vaccine strains. All viruses show susceptibility to neuraminidase inhibitors and baloxavir marboxil, which is important in situations of incidental human infections.
UNASSIGNED: The detection of virulence markers and accessory proteins in the analysed viruses suggests their higher propensity for replication in mammalian cells, increased virulence, and potential for transmission to humans, and implies compromised efficacy of influenza vaccines.