猪甲型流感病毒(SIV)既是对养猪业具有经济意义的病原体,也是可能传播给人类的潜在人畜共患生物。我们在这里描述了HA2的N端B环和CD螺旋在猪甲型流感病毒复制中的作用的详细表征。我们的实验结果表明,猪流感病毒的血凝素(HA)蛋白可以耐受功能保守的B环和CD螺旋中的某些突变。这些突变,然而,在细胞系和猪原代气管上皮细胞中具有实质上减毒的流感病毒复制。重要的是,我们发现一些B环或CD螺旋突变产生的病毒突变体在MDCK和ST细胞系中复制,但在原代气管上皮细胞中未能复制,因此表明猪HA蛋白可能是一种病毒毒力和致病因子。所描述的突变可以作为减毒疫苗候选物进一步探索,其可以有效地防止或消除流感病毒在猪群内和猪群之间的传播。
Swine influenza A virus (SIV) is both a pathogen of economic significance to the swine industry and a potential zoonotic organism that may be transmitted to humans. We described here the detailed characterization of a role of N-terminal B-loop and CD helix of HA2 in swine influenza A virus replication. Results of our experiments demonstrated that Hemagglutinin (HA) protein of swine influenza virus could tolerate some mutations in functionally conserved B-loop and CD helix. These mutations, however, have substantially attenuated influenza virus replication in both cell lines and porcine primary tracheal epithelial cells. Significantly, we found that some B-loop or CD helix mutations generated virus mutants that replicated in MDCK and ST cell lines but failed to replicate in primary tracheal epithelial cells, thereby suggesting that swine HA protein may function as a viral virulence and pathogenesis factor. The described mutations may be further explored as attenuated vaccine candidates that can effectively prevent or eliminate the spread of influenza virus within and between swine herds.