【Objective】 To evaluate the potential association of the molecular characteristics of avian influenza A H7N9 virus with its pathogenicity and patients’ clinical outcome by comparing the molecular differences between the two avian influenza A H7N9 virus strains isolated from the fatal case and the patient showing mild disease with full genome sequences

so as to provide further evidence for better understanding of the pathogenesis of avian influenza A H7N9 virus. 【Methods】 The two virus strains isolated from the fatal case and the patient showing mild disease were subjected to whole genome sequencing. The genome characteristics

the evolutionary relationship

the receptor binding sites

host specificity

virulence

drug resistance and potential glycosylated sites were analyzed by bioinformatics software. The sequences of avian influenza A H7N9 viruses isolated from the deceased and the recovered patients during 2013 and 2014 were downloaded from The Global Initiative on Sharing All Influenza Data (GISAID)

and the pivotal sites were compared to elucidate their relationship with the pathogenicity and the clinical outcome. 【Results】 The HA?NA and M gene of the two virus strains clustered with original novel avian influenza A H7N9 virus circulating in East China in 2013

while the NP

NS

PA

PB1 and PB2 gene originated from avian influenza H9N2 virus circulating in the poultry of Guangdong in 2013 . The mutation rate of L336M in PA and I368V in PB1 were increasing with time and had geographic differences. The two virus strains had over 99.2% nucleotide identity and 99.5% amino acid identity

but also showed several amino acid differences. Receptor binding sites exhibited one amino acid difference(226L and 226Q). Site 591 and site 627 in PB2 related to host specificity were different (591L and 591Q

627E and 627K). Site 353 in PA and site 627 in PB2 associated with virulence were distinct (353R and 353K

627E and 627K). The M2 protein of both virus strains had S31N mutation. All potential glycosylation motifs were relatively conservative. The mutation rate of PB2-E627K substitution of all the avian influenza A H7N9 viruses isolated from the fatal cases reported from 2013 until October 2014 was higher than the viruses isolated from the recovered cases. 【Conclusions】 The emergence of the two avian influenza A H7N9 virus strains in Guangdong may due to the further reassortments between the original novel avian influenza A H7N9 virus circulating in East China and the avian influenza H9N2 virus circulating in the poultry of Guangdong. The avian influenza A H7N9 virus was evolving because of the frequent reassortments and the increasing and geographic mutations of several key sites. Therefore

it is necessary to monitor its evolution and prevent a potential outbreak. The two virus strains

with different clinical outcomes

shared high sequence similarity

but also had differences in some pivotal sites. The mutation E627K in PB2 might be associated with the pathogenicity and the clinical outcome.