Reassortment and adaptive mutations of an emerging avian influenza virus H7N4 subtype in China

Abstract

Human infections with avian influenza viruses including H5, H7 and H9 hemagglutinin subtypes occur at a low rate. Among human infections with H7 viruses, regional outbreaks with H7N2, H7N3, H7N7 and H7N9 have been documented. Early in 2018, a human infection with a novel H7N4 avian influenza virus was reported in Jiangsu, China. This study is aimed at understanding the probable origin and molecular features of this emerging H7N4 virus. Genomic segments encoding hemagglutinin (HA) and neuraminidase (NA) of H7Nx and HxN4 viruses were compared with this H7N4 strain by alignment and phylogenetic tree analysis. Phylogenetic analysis indicated that the human H7N4 virus probably originated from multiple reassortments of avian H7N7 and H8N4 viruses for its HA and NA, respectively, and likely a regional uncharacterized virus for its internal segments. Our data excluded that circulating avian H9N2 viruses were the origin of the H7N4 internal segments, unlike the human H5N1 and H7N9 viruses that both had H9N2 backbones. This index case provided a unique opportunity to examine viral mutations by directly comparing the human isolate with its closest viral relatives isolated from avian species from the patient's farm, which may suggest critical mutations required for viral adaptation in humans. Whole-genome scanning was performed and the sequences of the human and related avian H7N4 isolates were compared. Mutations in PB2 (E627K), PB2 (K683T), PB1-F2 (N47S), HA (N283D), HA(K321E), NA(A137V), NA(K296R) and M2 (C19Y) were identified in the human isolate while no mutations were found in PB1, NP, NS1, and NS2 of the human H7N4 compared to the avian H7N4 viruses. Our data in this report provide further evidence for the genesis of this novel H7N4 virus with a multi-reassortment model and show molecular changes that might be responsible for the transmission of this virus from chickens or ducks to and subsequent replication in humans.

RIGI, TLR7, and TLR3 Genes Were Predicted to Have Immune Response Against Avian Influenza in Indigenous Ducks

“…The major concern is that genetic reassortment and adaptive mutation of avian influenza virus give rise to human influenza virus strain H7N4 ( Jiao et al, 2012 ; Ayora-Talavera, 2018 ; Karen, 2018 ; Li et al, 2020 ). The WHO has also warned about the pandemic on human flu resulting from genetic reassortment of avian influenza ( Qu et al, 2020 ). We observed in this study that the H5N1 strain of avian influenza, a highly pathogenic strain, was genetically closer to H6N2.…”

Genome-Wide Reassortment Analysis of Influenza A H7N9 Viruses Circulating in China during 2013–2019

“…Nonetheless, the H7N9 virus has continually undergone reassortment with other subtypes of AIVs since its emergence, such as seasonal influenza A virus H1N1, H3N2, and even influenza B virus [18][19][20], H5N6 [21,22], H6Ny [22,23], H9N2 [23][24][25][26][27][28], and even H7N9 itself [29]. As a result, multiple novel viruses were generated, including H7N2 [30], H7N3 [31], H7N4 [32], and H7N6 [33]. However, most of these reassortants were transient except for the progeny viruses with the H9N2 (especially the G57 or S genotype H9N2 [34]).…”

Pathogenesis and genetic characteristics of a novel reassortant low pathogenic avian influenza A(H7N6) virus isolated in Cambodia in 2019

“…Genetically similar A(H7N4) viruses were detected subsequently in poultry kept in the patient's backyard, confirming that the infection was zoonotic. Phylogenetic analyses indicated that the hemagglutinin (HA) gene of novel A(H7N4) viruses is distant from that of recent human and avian A(H7N9) viruses circulating in China, suggesting that these viruses probably originated from multiple reassortments of AIVs in wild waterfowl (Qu et al, 2020). Moreover, 2 months after the A(H7N4) human infection case in China, novel A(H7N4) viruses were detected in ducks from LBMs in Cambodia (Vijaykrishna et al, 2019).…”