Screening Influenza Virus Antibody And Study Specificity Of HA Binding With Reseptor

Influenza,referred to as the flu that is an acute,highly contagious disease caused by influenza viruses and often results in epidemics or pandemics among humans and animals.Influenza viruses can be divided into A,B,C and D types,and influenza A virus pose the greatest threat to human,which has caused several pandemic in the crowd.Influenza A virus can be divided into many subtypes which any combination of these two subtypes of HA and NA.HA can be divided into 18 subtypes which are H1?H18;NA can be divided into 11 subtypes which are N1?N11.Influenza virus identify the host cell surface sialic acid receptors specifically.Sialic acid receptors of different host cells are not the same linkage,the most sialic acid receptor on the human upper respiratory tract,which is a-2,6 linkage.While,on the avian upper respiratory tract the most sialic acid receptor is a-2,3 linkage.Human influenza virus mainly choose and bind ?-2,6 linkage sialic acid receptor,whereas avian influenza virus mainly choose and bind ?-2,6 linkage sialic acid receptor.People will be infected occasionally by avian influenza virus,if you often close contact with avian long time.Because of human down respiratory tract have many ?-2,3 linkage sialic acid receptors.For years the H5,H7,H9 subtypes have been reported to cause sporadic infections in humans.Furthermore when some amino acid of receptor binding region mutations,it maybe cause that avian influenza viruses prefer binding a-2,6 receptors and so the avian influenza virus can also infect humans.To date,only the H1,H2,and H3 subtypes of influenza A viruses have adapted to humans,causing annual seasonal flu worldwide.The 2009 H1N1 influenza global pandemic caused 1.85 million people deaths.After that the pandemic H1N1 substitute the previous seasonal influenza H1N1,which spread in thecrowds.Vaccine is still the most effective way to prevent influenza virus,but vaccine's protective efficacy on high-risk groups(infants,the elderly,and immune deficiency type)is low,the evolution of the virus results in the reduce or disappear of vaccines protect effect gradually.In the early stages of an influenza pandemic,influenza virus drugs may play a role.But antiviral drugs has shortcomings,such as the limited number of antiviral drugs,use of antiviral drugs lead to the emergence of drug-resistant strains,so it is particularly important to develop multiple drugs.Antibody therapy is a kind of new method of anti influenza virus.In recent years,antibodies which can neutralize broad spectrum of influenza virus were found constantly,some of them bind the head area of HA,some bind the neck area of HA.In the topic we obtain a humanized neutralizing antibody 1016 of influenza virus by high-throughput sequencing technology and information analysis angle.It can neutralize pandemic virus A/California/04/09 in vitro,but can't neutralize two viruses of A/Tianj in/15/09 and A/Puerto Rico/8/34.It is proved that antibody contact with HA head domain by hemagglutination inhibition(HI)experiment.We test antibody 1016 functions,at the same time we are screening the complex crystal of 1016 with HA protein.H3N2 virus antigen drift in 2014-2015 Seasonal influenza,which lead to the protective efficacy of the vaccine reduced.It is results that 594 people died from H3N2 in Hong Kong.This year H3N2 mainly is divided into 3C.3a and 3C.3a two clades by HA sequence phylogenetic analysis.We choose two typical viruses to research,which are A/Hong Kong/7278/2014 and A/Hong Kong/7276/2014.First,we express the extracellular domain of the corresponding HA.And then,we research the receptor binding characteristics of HA by Surface Plasmon resonance(SPR)test,tissue staining and mutant test.