Evolutionary dynamics of the H7N9 avian influenza virus based on large-scale sequence analysis

Since 2013, epidemics caused by novel H7N9 avian influenza A viruses (AIVs) have become a considerable public health issue. This study investigated the evolution of these viruses at the population level. Compared to H7 and N9 before 2013, there were 18 and 24 substitutions in the majority of novel H7N9 AIVs, respectively. Nine of these in HA and six in NA were rare before 2013, and four of these in HA and two in NA displayed host tropism. S136(128)N and A143(135)V are located on the receptor binding sites of the HA1 subunit and might be important factors in determining the host species of novel H7N9 AIV. On an overall scale, the evolution of H7 and N9, both in terms of time distribution and host species, is under negative selection. However, both in HA and NA, several sites were under positive selection. In both the overall epidemics and the human-derived H7N9 AIVs, eight positive selection sites were identified in HA1, with some located within the known antigen epitopes or the receptor binding site(RBS) domain. This may induce variations in H7N9 AIV with positive selection. It is necessary to strengthen the surveillance of novel H7N9 AIVs, both in human and bird population to determine whether a new virus has emerged through selection pressure and to prevent future epidemics from occurring.

自2013年以来，由新型甲型H7N9禽流感病毒（novel H7N9 avian influenza A viruses, AIVs）引发的疫情已成为一项严峻的公共卫生议题。本研究从种群层面探究了此类病毒的演化规律。与2013年前的H7和N9亚型病毒相比，多数新型H7N9禽流感病毒的血凝素（hemagglutinin, HA）与神经氨酸酶（neuraminidase, NA）基因分别存在18处和24处氨基酸取代。上述取代中，有9处位于HA基因、6处位于NA基因，在2013年前极为罕见；另有4处HA位点与2处NA位点呈现出宿主嗜性特征。S136(128)N与A143(135)V突变位点位于HA1亚基的受体结合区域，可能是决定新型H7N9禽流感病毒宿主物种范围的关键因素。整体而言，无论从时间分布还是宿主物种维度考量，H7与N9亚型病毒的演化均处于负选择压力之下。然而，HA与NA基因中均存在多个受正选择压力作用的位点。在整体疫情序列与人类来源的H7N9禽流感病毒序列中，HA1区域共鉴定出8个正选择位点，其中部分位点位于已知的抗原表位或受体结合结构域（RBS）内。这可能促使携带正选择突变的H7N9禽流感病毒发生变异。因此，有必要加强针对人类与禽类种群中新型H7N9禽流感病毒的监测工作，以判断是否因选择压力催生了新型病毒，并防范未来疫情的暴发。