Human infection caused by an avian influenza A (H7N9) virus with a polybasic cleavage site in Taiwan, 2017

On February 4, 2017, the Centers for Disease Control, Taiwan reported the year's first laboratory-confirmed human infection with avian influenza A (H7N9) virus, by three real-time reverse transcriptase polymerase chain reactions targeting three different segments of the matrix (M), hemagglutinin (HA), and neuraminidase (NA) genes.The patient is a 69-year old man who returned from the Guangdong province of mainland China and is currently in critical condition.The avian influenza A virus was first identified in March 2013 in China, and it was found to cause a severe infection in humans. 1 In this report, the virus (A/ Taiwan/1/2017) was isolated from a sputum specimen of the patient by inoculating into embryonated chicken eggs.The full-length genomic sequences were analyzed to investigate the phylogenetic and genetic characteristics of this virus (GISAID accession numbers EPI917062-EPI917069).We constructed the phylogenetic trees for each genome segment using the program MEGA6 (Tempe, Arizona, United States).Based on the analyzed phylogenies, the A/Taiwan/ 1/2017 virus is a novel reassortant belonging to a genotype whose genetic constellation has not been reported previously.The HA and NA genes of this virus belong to the Yangtze River Delta lineage, along with the H7N9 viruses isolated from Jiangsu, Zhejiang, and Fujian provinces of China in 2016 and 2017.This lineage is distinguished from the Pearl River Delta lineage that mainly comprises the virus strains isolated from Hong Kong and Guangdong province since 2014.Phylogenies of the six internal genes of A/Taiwan/1/2017 revealed the viral PB1 and MP (matrix protein) genes located at clades together with those of the A/Anhui/1/2013 vaccine strain and recently isolated viruses from Jiangsu, Zhejiang, Fujian, and Guangdong provinces in 2016 and 2017.The PB2 (polymerase basic protein 2), PA (polymerase acidic protein), and NS (non-structural protein) genes clustered together with early H7N9 viruses and could be separated from those of the 2016 and 2017 viruses.These results indicate that the H7N9 viruses are continuously evolving through reassortment.The molecular signatures of the A/Taiwan/1/2017 virus associated with host adaptation, receptor specificity, pathogenesis, and antiviral resistance were also investigated (Table 1).The Q226L/I and G228S substitutions in the HA protein, which are the major two mutations contributing to the high-affinity binding of viruses to human receptors, were not identified in this virus.However, several substitutions in HA were detected, namely S138A, T160A, and G186V.Of particular note, the A/Taiwan/1/2017 virus has an insertion of three basic amino acid residues (RKR) at the cleavage site connecting the HA1 and HA2 peptide regions, carrying a signature (PKRKRTAR/GLF) of highly pathogenic avian influenza (HPAI) viruses.This has been the first demonstration of Conflicts of interest: The authors have no conflicts of interest relevant to this article.