The S190R mutation in the hemagglutinin protein of pandemic H1N1 2009 influenza virus increased its pathogenicity in mice

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.

MODELING STRATEGIES FOR CONTROLLING H1N1 OUTBREAKS IN CHINA

There has been a global attack of A/H1N1 virus in 2009, which widely affected the world＇s normal stability and economic development. Since the emergence of the first diagnosed A/H1N1 influenza infected person in 11 May 2009 in China, very strict policy including quarantine and isolation measures were widely implemented to control the spread of this disease before the vaccine appeared. We propose a compartmental model that mimics the infection process of A/H1N1 under control strategies taken in China's Mainland. Apart from theoretical analysis, using the statistic data of Shaanxi Province, we estimated the unknown epidemiological parameters of this disease in Shaanxi via least-squares fitting method. The estimated control reproductive number of H1N1 for its first peak was Rc1 = 2.555 （95% CI： 2.362 2.748） and that for the second peak was Rc2 = 1.886 （95% CI： 1.765-2.001）. Our findings in this paper suggest that neither quarantine nor isolation measures could be relaxed, and the implementation of these interventions can reduce the pandemic outbreak of A/H1N1 pandemic significantly.