The Impact of NA Stalk Deletion on HA Receptor Binding Specificity of Avian H7N9 in China in 2013-14 and Avian H7N7 in Netherlands in 2003

摘要

A novel avian origin influenza H7N9 virus emerged in March 2013 in China and caused severe disease in humans. The high human death rate has caused public health concern and attracted global attention. The influenza viruses have two surface proteins: hemagglutinin (HA) and neuraminidase (NA), with HA facilitating viral entry into a host cell and NA helping new viral particles leave a host cell to infect more host cells. In a previous study published in May 2003, we applied computational analysis to the HA sequences of this new virus. Our findings suggested that the HA of this virus had avian type receptors as its primary binding and human types as secondary binding, which was verified by several subsequent wet lab experiments in later months of 2013. We also showed that the human H7N9 and avian H7N9 in China in 2013 shared the same HA receptor binding patterns. The NA protein of this new virus has a stalk deletion that is associated with virulence and host adaptation. In the present study, we wanted to understand the biological effects of this NA deletion on the HA receptor binding preference of this virus. However, the NA proteins of human H7N9 in China in 2013 all carry a stalk deletion so we lack the NA proteins with no stalk deletion as a control. In this study, we chose instead the NA proteins of avian H7N9 in China in 2013-14 and those of avian H7N7 in Netherlands in 2003 as some of them had a NA stalk deletion and some did not. We sought to employ a computational approach to revealing the impact of this NA stalk deletion on HA receptor binding preference of this virus. Our analysis implied that this deletion in the stalk region of NA enhanced the human receptor binding of avian H7N9 in China in 2013-14 and avian H7N7 in the Netherlands in 2003.