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New hemagglutinin dual-receptor-binding pattern of a human-infecting influenza A (H7N9) virus isolated after fifth epidemic wave.

ABSTRACT: Since 2013, influenza H7N9 virus has caused five epidemic waves of human infection. The virus evolved from low pathogenic to highly pathogenic in wave 5, 2017, while the prevalence of host receptor-binding tropism in human-infecting viruses maintained dual-receptor-binding property with preference for avian receptor. A human-infecting H7N9 virus was isolated after the fifth epidemic wave and possessed an avian and human dual-receptor specificity, with a moderately higher affinity for human receptor binding. A V186I (H3 numbering) substitution in the receptor-binding site of the hemagglutinin (HA) molecule is responsible for the alteration of the dual-receptor-binding tropism. Viral strains which contain I186 amino acid of avian- and human-infecting H7N9 viruses were all isolated during or after wave 5, and their HA genes clustered in a same phylogenetic clade together with 2018-9 H7N9 isolates, highlights a new evolutionary path for human adaption of natural H7N9 viruses.

SUBMITTER: Guo L

PROVIDER: S-EPMC7169767 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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New hemagglutinin dual-receptor-binding pattern of a human-infecting influenza A (H7N9) virus isolated after fifth epidemic wave.

Guo Lei L Li Nan N Li Wenlong W Zhou Jienan J Ning Ruotong R Hou Min M Liu Longding L

Virus evolution 20200101 1

Since 2013, influenza H7N9 virus has caused five epidemic waves of human infection. The virus evolved from low pathogenic to highly pathogenic in wave 5, 2017, while the prevalence of host receptor-binding tropism in human-infecting viruses maintained dual-receptor-binding property with preference for avian receptor. A human-infecting H7N9 virus was isolated after the fifth epidemic wave and possessed an avian and human dual-receptor specificity, with a moderately higher affinity for human recep ...[more]

PMID: 32337071

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Project description:The fifth wave of the H7N9 influenza epidemic in China was distinguished by a sudden increase in human infections, an extended geographic distribution, and the emergence of highly pathogenic avian influenza (HPAI) viruses. Genetically, some H7N9 viruses from the fifth wave have acquired novel amino acid changes at positions involved in mammalian adaptation, antigenicity, and hemagglutinin cleavability. Here, several human low-pathogenic avian influenza (LPAI) and HPAI H7N9 virus isolates from the fifth epidemic wave were assessed for their pathogenicity and transmissibility in mammalian models, as well as their ability to replicate in human airway epithelial cells. We found that an LPAI virus exhibited a similar capacity to replicate and cause disease in two animal species as viruses from previous waves. In contrast, HPAI H7N9 viruses possessed enhanced virulence, causing greater lethargy and mortality, with an extended tropism for brain tissues in both ferret and mouse models. These HPAI viruses also showed signs of adaptation to mammalian hosts by acquiring the ability to fuse at a lower pH threshold than other H7N9 viruses. All of the fifth-wave H7N9 viruses were able to transmit among cohoused ferrets but exhibited a limited capacity to transmit by respiratory droplets, and deep sequencing analysis revealed that the H7N9 viruses sampled after transmission showed a reduced amount of minor variants. Taken together, we conclude that the fifth-wave HPAI H7N9 viruses have gained the ability to cause enhanced disease in mammalian models and with further adaptation may acquire the ability to cause an H7N9 pandemic.IMPORTANCE The potential pandemic risk posed by avian influenza H7N9 viruses was heightened during the fifth epidemic wave in China due to the sudden increase in the number of human infections and the emergence of antigenically distinct LPAI and HPAI H7N9 viruses. In this study, a group of fifth-wave HPAI and LPAI viruses was evaluated for its ability to infect, cause disease, and transmit in small-animal models. The ability of HPAI H7N9 viruses to cause more severe disease and to replicate in brain tissues in animal models as well as their ability to fuse at a lower pH threshold than LPAI H7N9 viruses suggests that the fifth-wave H7N9 viruses have evolved to acquire novel traits with the potential to pose a higher risk to humans. Although the fifth-wave H7N9 viruses have not yet gained the ability to transmit efficiently by air, continuous surveillance and risk assessment remain essential parts of our pandemic preparedness efforts.

Project description:H9N2 Avian influenza virus (AIV) is regarded as a principal donor of viral genes through reassortment to co-circulating influenza viruses that can result in zoonotic reassortants. Whether H9N2 virus can maintain sustained evolutionary impact on such reassortants is unclear. Since 2013, avian H7N9 virus had caused five sequential human epidemics in China; the fifth wave in 2016-2017 was by far the largest but the mechanistic explanation behind the scale of infection is not clear. Here, we found that, just prior to the fifth H7N9 virus epidemic, H9N2 viruses had phylogenetically mutated into new sub-clades, changed antigenicity and increased its prevalence in chickens vaccinated with existing H9N2 vaccines. In turn, the new H9N2 virus sub-clades of PB2 and PA genes, housing mammalian adaptive mutations, were reassorted into co-circulating H7N9 virus to create a novel dominant H7N9 virus genotype that was responsible for the fifth H7N9 virus epidemic. H9N2-derived PB2 and PA genes in H7N9 virus conferred enhanced polymerase activity in human cells at 33°C and 37°C, and increased viral replication in the upper and lower respiratory tracts of infected mice which could account for the sharp increase in human cases of H7N9 virus infection in the 2016-2017 epidemic. The role of H9N2 virus in the continual mutation of H7N9 virus highlights the public health significance of H9N2 virus in the generation of variant reassortants of increasing zoonotic potential.IMPORTANCEAvian H9N2 influenza virus, although primarily restricted to chicken populations, is a major threat to human public health by acting as a donor of variant viral genes through reassortment to co-circulating influenza viruses. We established that the high prevalence of evolving H9N2 virus in vaccinated flocks played a key role, as donor of new sub-clade PB2 and PA genes in the generation of a dominant H7N9 virus genotype (G72) with enhanced infectivity in humans during the 2016-2017 N7N9 virus epidemic. Our findings emphasize that the ongoing evolution of prevalent H9N2 virus in chickens is an important source, via reassortment, of mammalian adaptive genes for other influenza virus subtypes. Thus, close monitoring of prevalence and variants of H9N2 virus in chicken flocks is necessary in the detection of zoonotic mutations.

Dataset Information

New hemagglutinin dual-receptor-binding pattern of a human-infecting influenza A (H7N9) virus isolated after fifth epidemic wave.

Publications

New hemagglutinin dual-receptor-binding pattern of a human-infecting influenza A (H7N9) virus isolated after fifth epidemic wave.

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