During 2013, three new avian influenza A virus subtypes, A(H7N9), A(H6N1), and A(H10N8), resulted in human infections.While the A(H7N9) virus resulted in a significant epidemic in China across 19 provinces and municipalities, both A(H6N1) and A(H10N8) viruses resulted in only a few human infections. This study focuses on the major surface glycoprotein hemagglutinins from both of these novel human viruses. The detailed structural and glycan microarray analyses presented here highlight the idea that both A(H6N1) and A(H10N8) virus hemagglutinins retain a strong avian receptor binding preference and thus currently pose a low risk for sustained human infections.
IMPORTANCEHuman infections with zoonotic influenza virus subtypes continue to be a great public health concern. We report detailed structural analysis and glycan microarray data for recombinant hemagglutinins from A(H6N1) and A(H10N8) viruses, isolated from human infections in 2013, and compare them with hemagglutinins of avian origin. This is the first structural report of an H6 hemagglutinin, and our results should further the understanding of these viruses and provide useful information to aid in the continuous surveillance of these zoonotic influenza viruses.
Based on the serological reactivity of influenza A virus surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), 18 HA (H1 to H18) and 11 NA (N1 to N11) variants have been identified in aquatic birds and bats (1-3). The Centers for Disease Control and Prevention estimates that annually, seasonal influenza viruses can infect up to 20% of the human population (http: //www.cdc.gov/flu). In the United States alone, estimates of influenza-associated deaths range from 3,000 to 49,000 per annum (4). In the last 100 years, three influenza virus subtypes have successfully adapted to the human population, causing four pandemics: H1N1 in 1918 and 2009, H2N2 in 1957, and H3N2 in 1968 (5-8). Avian influenza viruses have become endemic in domestic poultry in certain parts of the world, and a growing number of human cases of avian influenza infection with different subtypes [A(H5N1), A(H5N6), A(H7N2), A(H7N3), A(H7N7), and A(H9N2)] have been reported in recent years (9-14), causing significant public health concern.During 2013, three novel avian influenza A viruses, A(H7N9), A(H10N8), and A(H6N1), were isolated from human patients. The first human infection with an avian influenza A(H7N9) virus was reported in March 2013 near Shanghai, China, and its emergence led to a human epidemic in that country (15). Indeed, as of October 2014, the virus had spread widely to a number of provinces and municipalities in China and resulted in over 450 human cases, with an ϳ38% mortality rate. Not surprisingly, most research has focused on this A(H7N9) virus due to its rapid spread and severity. Whole-genome genetic analysis highlighted the fact that the six internal genes of the virus all originated from H9N2 viruses and may contribute to the increased pathogenicity observed in human infections (16).In mid-201...