The Genetic Evolution Of H7N9 Influenza Virus

In 2013,human infection with H7N9 avian influenza A virus(AIV)were first reported in China,five epidemic waves have been formed in Chinese population.The H7N9 virus that appeared before the fifth wave of epidemics belonged to low pathogenic avian influenza,but during the fifth wave of epidemics,it was found that some H7N9 virus transformed into highly pathogenic avian influenza.The HP H7N9 caused large-scale deaths of poultry,led to a significant increase in human infections.According to statistics,766 cases of human infection were reported in the fifth wave of H7N9 epidemics,exceeding all previous peaks.This raises an alarm about the potential of H7N9 to become a pandemic problem.Therefore,in order to deal with the potential threat caused by the rapid evolution of the H7N9 avian influenza virus more effectively and to avoid the occurrence of a pandemic,it is important to continuously monitor the evolution and transmission of the H7N9 virus.Molecular mechanisms that enable AIVs to cross the species-barrier and allow efficient transmission in mammals have been studied widely,and many amino acid changes have been suggested to play roles in these processes.So we evaluated the potential of H7N9 AIVs to drive pandemic events.Our compilation of the amino acid changes required for AIVs to cross the species-barrier discovers 58 changes that have very high proportions in both the human-and avian-isolated H7N9 viruses.These changes correspond with sporadic human infections that continue to occur in regions of avian infections.Among the six internal viral genes,amino acid changes do not differ significantly between H9N2 and H7N9,except for V100 A in PA,and K526 R,D627K,and D701 N in PB2.H9N2 AIVs provide internal genes to H7N9.Most of the amino acid changes in H7N9 appear to come directly from H9N2.Seventeen amino acid substitutions appear to have fixed quickly by the 5th wave.Among these,six amino acid sites in HA1 are receptor binding sites,and PB2-A588 V was shown to promote the adaptation of AIVs to mammals.The accelerated fixation of mutations may promote the adaptation of H7N9 to human,but need further functional evidence.It is necessary for us to monitor the H7N9 AIVs continuously.Generally,the H7N9 AIVs was mainly transmitted in chickens and cannot be effectively replicated in ducks.However,many studies indicates that the highly pathogenic H7N9 virus has extended its host range by acquiring genes from duck influenza viruses and is adapting to ducks now.This may be a new challenge for the prevention and control of H7N9 AIVs.Therefore,we further carried out a systematic study of the H7 AIVs isolated from ducks.We found that although ducks are not the major host of 2013 H7N9,a duck H7 lineage which is distant from the 2013 H7N9 viruses is circulating in ducks in China.Whether these H7 viruses can contribute their genes to chicken H7N9 should raise our attention.Thus,we collected all available H7N9 sequences to detect potential novel reassortments of the H7N9 AIVs,and found evidences that three human-isolated H7N9 obtained internal genes from duck and human AIVs.This suggest that surveillance and control of duck AIVs is critical for the control of H7N9 viruses,which was almost ignored previously.The reassortments between 2013 H7N9 and duck AIVs would further raise the diversity and spread of the H7N9,and thus raise great thread to the public health.This study revealed the characteristics and rules of the H7N9 AIVs in the process of evolution and transmission from the perspective of evolutionary biology.The research results deepen the understanding of the evolution and spread of avian influenza virus and play an important role in assessing the trend of the epidemic situation.It’s also benefit to quickly identify the source of infectious diseases from animals.