Human influenza viruses preferentially bind to sialic acid-α2,6-galactose (SAα2,6Gal) receptors, which are predominant in human upper respiratory epithelia, whereas avian influenza viruses preferentially bind to SA...Human influenza viruses preferentially bind to sialic acid-α2,6-galactose (SAα2,6Gal) receptors, which are predominant in human upper respiratory epithelia, whereas avian influenza viruses preferentially bind to SAα2,3Gal receptors. However, variants with amino acid substitutions around the receptor-binding sites of the hemagglutinin (HA) protein can be selected after several passages of human influenza viruses from patients’ respiratory samples in the allantoic cavities of embryonated chicken eggs. In this study, we detected an egg-adapted HA S190R mutation in the pandemic H1N1 virus 2009 (pdmH1N1), and evaluated the effects of this mutation on receptor binding affinity and pathogenicity in mice. Our results revealed that residue 190 is located within the pocket structure of the receptor binding site. The single mutation to arginine at position 190 slightly increased the binding affinity of the virus to the avian receptor and decreased its binding to the long human α2,6-linked sialic acid receptor. Our study demonstrated that the S190R mutation resulted in earlier death and higher weight loss in mice compared with the wild-type virus. Higher viral titers at 1 dpi (days post infection) and diffuse damage at 4 dpi were observed in the lung tissues of mice infected with the mutant virus.展开更多
Dear Editor,Influenza A viruses cause pandemics at an interval of approximately 10-40 years,and pigs are regarded as a"mixing vessel"because they are easily infected with avian and human influenza viruses(Ito et al...Dear Editor,Influenza A viruses cause pandemics at an interval of approximately 10-40 years,and pigs are regarded as a"mixing vessel"because they are easily infected with avian and human influenza viruses(Ito et al.,1998).According to previous studies,H3N2,H1N2,and H1N1 subtypes o(swine influenza viruses have been detected in Korean pigs (Pascua et al., 2013; Kim et al., 2014; Song et al., 2007). Moreover, a novel H3N2 influenza virus containing the matrix (34) gene from a 2009 pandemic influenza virus was detected in Korean pigs in 2013 (Pascua et al., 2013), an H1N2 influenza virus con- taining the internal genes from a 2009 pandemic influ- enza virus was found in Korean pigs in 2014 (Kim et al., 2014), and an H1N1 influenza virus containing all genes from the classical swine influenza viruses was isolated from Korean pigs in 2007 (Song et al., 2007).展开更多
基金supported by the National Key Research and Development Program of China(2016YFC1200201 to Yuelong Shu)the National Mega-projects for Infectious Diseases(2014ZX10004002002 to Yuelong Shu)the young scientist fund of Chinese Center for Disease Control and Prevention(2016A103 to Wenfei Zhu)
文摘Human influenza viruses preferentially bind to sialic acid-α2,6-galactose (SAα2,6Gal) receptors, which are predominant in human upper respiratory epithelia, whereas avian influenza viruses preferentially bind to SAα2,3Gal receptors. However, variants with amino acid substitutions around the receptor-binding sites of the hemagglutinin (HA) protein can be selected after several passages of human influenza viruses from patients’ respiratory samples in the allantoic cavities of embryonated chicken eggs. In this study, we detected an egg-adapted HA S190R mutation in the pandemic H1N1 virus 2009 (pdmH1N1), and evaluated the effects of this mutation on receptor binding affinity and pathogenicity in mice. Our results revealed that residue 190 is located within the pocket structure of the receptor binding site. The single mutation to arginine at position 190 slightly increased the binding affinity of the virus to the avian receptor and decreased its binding to the long human α2,6-linked sialic acid receptor. Our study demonstrated that the S190R mutation resulted in earlier death and higher weight loss in mice compared with the wild-type virus. Higher viral titers at 1 dpi (days post infection) and diffuse damage at 4 dpi were observed in the lung tissues of mice infected with the mutant virus.
基金in part funded by a 2015 research fund from Chungnam National University
文摘Dear Editor,Influenza A viruses cause pandemics at an interval of approximately 10-40 years,and pigs are regarded as a"mixing vessel"because they are easily infected with avian and human influenza viruses(Ito et al.,1998).According to previous studies,H3N2,H1N2,and H1N1 subtypes o(swine influenza viruses have been detected in Korean pigs (Pascua et al., 2013; Kim et al., 2014; Song et al., 2007). Moreover, a novel H3N2 influenza virus containing the matrix (34) gene from a 2009 pandemic influenza virus was detected in Korean pigs in 2013 (Pascua et al., 2013), an H1N2 influenza virus con- taining the internal genes from a 2009 pandemic influ- enza virus was found in Korean pigs in 2014 (Kim et al., 2014), and an H1N1 influenza virus containing all genes from the classical swine influenza viruses was isolated from Korean pigs in 2007 (Song et al., 2007).