Emergence of Influenza A(H7N4) Virus, Cambodia

Vijaykrishna, Dhanasekaran; Deng, Yi‐Mo; Grau, Miguel L.; Kay, Matthew; Suttie, Annika; Horwood, Paul F.; Kalpravidh, Wantanee; Claes, Filip; Osbjer, Kristina; Dussart, Philippe; Barr, Ian G.; Karlsson, Erik A.

doi:10.3201/eid2510.190506

Cited by 10 publications

(15 citation statements)

References 8 publications

(13 reference statements)

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“…A single human non-fatal infection with an A/H7N4 subtype virus occurred in an elderly woman in Jiangsu, China in December 2017 [192, 196]. This virus is antigenically distinct from formerly circulating A/H7 strains, and, concerningly, appears to be spreading across Southeast Asia, continually reassorting with other viruses in the region [197, 198]. To date, none of the novel A/H7N4 viruses contains known amino acid mutations that confer adaptation of AIV to humans (e.g., PB2 627/701 or HA 186/226/228) or antiviral resistance.…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…To date, none of the novel A/H7N4 viruses contains known amino acid mutations that confer adaptation of AIV to humans (e.g., PB2 627/701 or HA 186/226/228) or antiviral resistance. However, A/H7N4 isolated from Cambodia does contain the M gene amino acid mutations N30D and T215A that increase pathogenicity of A/H5N1 virus in mice [198]. Due to the antigenic differences between the A/H7N4 viruses and other H7 lineages, including the A/Anhui/1/2013-like A/H7N9 lineage, the continual spread, and risk for human infection, this newly detected A/H7N4 lineage is now in preparation as a candidate vaccine virus for pandemic preparedness [199].…”

Section: Discussion/conclusionmentioning

confidence: 99%

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Inventory of molecular markers affecting biological characteristics of avian influenza A viruses

et al. 2019

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Avian influenza viruses (AIVs) circulate globally, spilling over into domestic poultry and causing zoonotic infections in humans. Fortunately, AIVs are not yet capable of causing sustained human-to-human infection; however, AIVs are still a high risk as future pandemic strains, especially if they acquire further mutations that facilitate human infection and/or increase pathogenesis. Molecular characterization of sequencing data for known genetic markers associated with AIV adaptation, transmission, and antiviral resistance allows for fast, efficient assessment of AIV risk. Here we summarize and update the current knowledge on experimentally verified molecular markers involved in AIV pathogenicity, receptor binding, replicative capacity, and transmission in both poultry and mammals with a broad focus to include data available on other AIV subtypes outside of A/H5N1 and A/H7N9.

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Section: Discussion/conclusionmentioning

confidence: 99%

Section: Discussion/conclusionmentioning

confidence: 99%

Inventory of molecular markers affecting biological characteristics of avian influenza A viruses

et al. 2019

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“…However, none of the genomic segments of the Cambodian H7N4 virus were similar to those of JS2018. That the novel human H7N4 virus in China may be more a strain of fitness for human infection remains to be studied [19]. Active surveillance and predictive evolutionary studies of the novel H7N4 viruses should be enhanced in East and Southeast Asia.…”

Section: Virusmentioning

confidence: 99%

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

Cardona

et al. 2020

PLoS ONE

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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.

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“…The highly pathogenic avian influenza virus (HPAIV) A/H5N1 subtype has been a major, global public health concern since it was first detected in humans in Asia in 1997. In addition, novel subtypes such as the A/H5Nx, clade 2.3.4.4, and A/H7Nx viruses continue to emerge in the region [1,2]. Although zoonotic infection of humans is relatively rare, 861 cases of HPAI A/H5N1 in humans have been reported, with a case fatality rate of 53% [3].…”

Section: Introductionmentioning

confidence: 99%

Transmission experiments support clade-level differences in the transmission and pathogenicity of Cambodian influenza A/H5N1 viruses

Horwood

Fabrizio

Horm

et al. 2020

Emerging Microbes & Infections

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Influenza A/H5N1 has circulated in Asia since 2003 and is now enzootic in many countries in that region. In Cambodia, the virus has circulated since 2004 and has intermittently infected humans. During this period, we have noted differences in the rate of infections in humans, potentially associated with the circulation of different viral clades. In particular, a reassortant clade 1.1.2 virus emerged in early 2013 and was associated with a dramatic increase in infections of humans (34 cases) until it was replaced by a clade 2.3.2.1c virus in early 2014. In contrast, only one infection of a human has been reported in the 6 years since the clade 2.3.2.1c virus became the dominant circulating virus. We selected three viruses to represent the main viral clades that have circulated in Cambodia (clade 1.1.2, clade 1.1.2 reassortant, and clade 2.3.2.1c), and we conducted experiments to assess the virulence and transmissibility of these viruses in avian (chicken, duck) and mammalian (ferret) models. Our results suggest that the clade 2.3.2.1c virus is more "avian-like," with high virulence in both ducks and chickens, but there is no evidence of aerosol transmission of the virus from ducks to ferrets. In contrast, the two clade 1 viruses were less virulent in experimentally infected and contact ducks. However, evidence of chicken-to-ferret aerosol transmission was observed for both clade 1 viruses. The transmission experiments provide insights into clade-level differences that might explain the variation in A/H5N1 infections of humans observed in Cambodia and other settings.

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Emergence of Influenza A(H7N4) Virus, Cambodia

Cited by 10 publications

References 8 publications

Inventory of molecular markers affecting biological characteristics of avian influenza A viruses

Inventory of molecular markers affecting biological characteristics of avian influenza A viruses

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

Transmission experiments support clade-level differences in the transmission and pathogenicity of Cambodian influenza A/H5N1 viruses

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