RESUMO
Avian influenza A virus continues to pose a global threat with occasional H5N1 human infections, which is emphasized by a recent severe human infection caused by avian-origin H7N9 in China. Luckily these viruses do not transmit efficiently in human populations. With a few amino acid substitutions of the hemagglutinin H5 protein in the laboratory, two H5 mutants have been shown to obtain an air-borne transmission in a mammalian ferret model. Here in this study one of the mutant H5 proteins developed by Kawaoka's group (VN1203mut) was expressed in a baculovirus system and its receptor-binding properties were assessed. We herein show that the VN1203mut had a dramatically reduced binding affinity for the avian α2,3-linkage receptor compared to wild type but showed no detectable increase in affinity for the human α2,6-linkage receptor, using Surface Plasmon Resonance techonology. Further, the crystal structures of the VN1203mut and its complexes with either human or avian receptors demonstrate that the VN1203mut binds the human receptor in the same binding manner (cis conformation) as seen for the HAs of previously reported 1957 and 1968 pandemic influenza viruses. Our receptor binding and crystallographic data shown here further confirm that the ability to bind the avian receptor has to decrease for a higher human receptor binding affinity. As the Q226L substitution is shown important for obtaining human receptor binding, we suspect that the newly emerged H7N9 binds human receptor as H7 has a Q226L substitution.
Assuntos
Humanos , Microbiologia do Ar , Cristalografia por Raios X , Glicosilação , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Química , Genética , Metabolismo , Virus da Influenza A Subtipo H5N1 , Química , Metabolismo , Subtipo H7N9 do Vírus da Influenza A , Química , Modelos Moleculares , Proteínas Mutantes , Química , Genética , Metabolismo , Ligação Proteica , Estabilidade Proteica , Receptores de Superfície Celular , Genética , Metabolismo , Solubilidade , Ressonância de Plasmônio de Superfície , TemperaturaRESUMO
Influenza virus is the causative agent of the seasonal and occasional pandemic flu. The current H1N1 influenza pandemic, announced by the WHO in June 2009, is highly contagious and responsible for global economic losses and fatalities. Although the H1N1 gene segments have three origins in terms of host species, the virus has been named swine-origin influenza virus (S-OIV) due to a predominant swine origin. 2009 S-OIV has been shown to highly resemble the 1918 pandemic virus in many aspects. Hemagglutinin is responsible for the host range and receptor binding of the virus and is therefore a primary indicator for the potential of infection. Primary sequence analysis of the 2009 S-OIV hemagglutinin (HA) reveals its closest relationship to that of the 1918 pandemic influenza virus, however, analysis at the structural level is necessary to critically assess the functional significance. In this report, we report the crystal structure of soluble hemagglutinin H1 (09H1) at 2.9 Å, illustrating that the 09H1 is very similar to the 1918 pandemic HA (18H1) in overall structure and the structural modules, including the five defined antiboby (Ab)-binding epitopes. Our results provide an explanation as to why sera from the survivors of the 1918 pandemics can neutralize the 2009 S-OIV, and people born around the 1918 are resistant to the current pandemic, yet younger generations are more susceptible to the 2009 pandemic.
Assuntos
Animais , Clonagem Molecular , Cristalografia por Raios X , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Química , Genética , Alergia e Imunologia , Vírus da Influenza A Subtipo H1N1 , Química , Genética , Alergia e Imunologia , Modelos Moleculares , Conformação Proteica , Suínos , VirologiaRESUMO
Objective: To study the therapeutic effects of Xuesaitong injections on senile coronary heart disease ( CHD) . Methods: Retired veteran cadres and their relations in our unit were enrolled in this study. They were divied into Xuesaitong treatment group (58 cases) and control group ( Salvia Miltiorrhi-za Compound Injections and Venoruton, 34 cases). Follow-up time was 10 days per period of treatment. The symptoms, ECG, serum cholesterol and triglyceride before and after treatment were compared. Results :ECG and serum lipids were significantly improved in Xuesaitong treatment group (P 0.05). Conclusion: Xuesaitong injections have therapeutic effects on senile CHD.