Biological characterisation of the emerged highly pathogenic avian influenza (HPAI) A(H7N9) viruses in humans, in mainland China, 2016 to 2017

Zhu, Wenfei; Zhou, Jianfang; Li, Zi; Yang, Lei; Li, Xiyan; Huang, Weijuan; Zou, Sumei; Chen, Wenbing; Wei, Hejiang; Tang, Jing; Liu, Liqi; Dong, Jie; Wang, Dayan; Shu, Yuelong

doi:10.2807/1560-7917.es.2017.22.19.30533

Cited by 109 publications

(108 citation statements)

References 10 publications

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“…To assess the pandemic potential of HPAI H7N9 viruses, we examined the biological properties of GD/3, an HPAI H7N9 virus isolated from a fatal human case treated with oseltamivir (Zhu et al, 2017). GD/3 does not encode the mammalian-adapting PB2-627K marker, but possesses an A588V substitution in PB2, which enhances H7N9 viral polymerase activity, replication in mammalian cells, and virulence in mice (Xiao et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

A Highly Pathogenic Avian H7N9 Influenza Virus Isolated from A Human Is Lethal in Some Ferrets Infected via Respiratory Droplets

Imai

Watanabe

Kiso

et al. 2017

Cell Host & Microbe

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SUMMARY Low pathogenic H7N9 influenza has recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient human-to-human transmissibility. We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants that represent neuraminidase inhibitor-sensitive and -resistant subpopulations detected within the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus, with the exception of the neuraminidase inhibitor-resistant virus, which showed mild-to-moderate attenuation. All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals. Neuraminidase inhibitors showed limited effectiveness against these viruses in vivo, but the viruses were susceptible to a polymerase inhibitor. These results suggest that the highly pathogenic H7N9 virus has pandemic potential and should be closely monitored.

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Section: Resultsmentioning

confidence: 99%

A Highly Pathogenic Avian H7N9 Influenza Virus Isolated from A Human Is Lethal in Some Ferrets Infected via Respiratory Droplets

Imai

Watanabe

Kiso

et al. 2017

Cell Host & Microbe

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129

135

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“…A number of oseltamivir-resistant clinical A(H7N9) isolates have been identified. Mutations in the NA that are associated with antiviral resistance in these viruses include E119V, I222R or I222K, A246T, and R292K (8,29,31,32). We rescued H6N9 AH/13 viruses that contained 119V, 222R, 246T, or 292K in the NA and tested the ability of MAbs 1E8, 2F6, 11B2, and 10F4 to inhibit their NA activity.…”

Section: Preparation Of N9 Mabs a Panel Of 19mentioning

confidence: 99%

“…Candidate vaccine viruses (CVVs) of A(H7N9) have been generated and tested for safety and immunogenicity (4)(5)(6) and could be authorized for use if needed. The most recent outbreak of A(H7N9) infection, i.e., the fifth epidemic wave, has increased the concern regarding the potential pandemic threat of this virus because the incidence rate has increased, A(H7N9) strains with hemagglutinins (HAs) that are antigenically distinct from the tested CVVs have emerged, and highly pathogenic strains have been isolated (7,8). There is therefore a need to consider additional ways to prevent and control A(H7N9) infection.…”

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confidence: 99%

Comparison of the Efficacy of N9 Neuraminidase-Specific Monoclonal Antibodies against Influenza A(H7N9) Virus Infection

Wan

Gao

et al. 2018

J Virol

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The fifth wave of A(H7N9) virus infection in China from 2016 to 2017 caused great concern due to the large number of individuals infected, the isolation of drug-resistant viruses, and the emergence of highly pathogenic strains. Antibodies against neuraminidase (NA) provide added benefit to hemagglutinin-specific immunity and may be important contributors to the effectiveness of A(H7N9) vaccines. We generated a panel of mouse monoclonal antibodies (MAbs) to identify antigenic domains on NA of the novel A(H7N9) virus and compared their functional properties. The loop formed in the region of residue 250 (250 loop) and the domain formed by the loops containing residues 370, 400, and 430 were identified as major antigenic regions. MAbs 1E8, 2F6, 10F4, and 11B2, which recognize these two antigenic domains, were characterized in depth. These four MAbs differ in their abilities to inhibit cleavage of small and large substrates (methyl-umbelliferylacetyl neuraminic acid [MU-NANA] and fetuin, respectively) in NA inhibition assays. 1E8 and 11B2 did not inhibit NA cleavage of either MU-NANA or fetuin, and 2F6 inhibited cleavage of fetuin alone, whereas 10F4 inhibited cleavage of both substrates. All four MAbs reduced the in vitro spread of viruses carrying either the wild-type N9 or N9 with antiviral-resistant mutations but to different degrees. These MAbs have different in vivo levels of effectiveness: 10F4 was the most effective in protecting mice against challenge with A(H7N9) virus, 2F6 was less effective, and 11B2 failed to protect BALB/c mice at the doses tested. Our study confirms that NA-specific antibodies can protect against A(H7N9) infection and suggests that in vitro properties can be used to rank antibodies with therapeutic potential. IMPORTANCEThe novel A(H7N9) viruses that emerged in China in 2013 continue to infect humans, with a high fatality rate. The most recent outbreak resulted in a larger number of human cases than previous epidemic waves. Due to the absence of a licensed vaccine and the emergence of drug-resistant viruses, there is a need to develop alternative approaches to prevent or treat A(H7N9) infection. We have made a panel of mouse monoclonal antibodies (MAbs) specific for neuraminidase (NA) of A(H7N9) viruses; some of these MAbs are effective in inhibiting viruses that are resistant to antivirals used to treat A(H7N9) patients. Binding avidity, inhibition of NA activity, and plaque formation correlated with the effectiveness of these MAbs to protect mice against lethal A(H7N9) virus challenge. This study identifies in vitro measures that can be used to predict the in vivo efficacy of NA-specific antibodies, providing a way to select MAbs for further therapeutic development.

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“…Compared to urban residents, rural residents usually have higher likelihood of exposure to sick or dead poultry, which were attributed to the popular country lifestyle of raising backyard poultry in China 5, 20, 21, 22. The human cases of infection with highly pathogenic avian influenza (HPAI) A(H7N9) virus have been found in Guangxi, Guangdong, and Hunan Provinces during the fifth wave 23, 24, 25. So far, there were no human cases of infection with HPAI A(H7N9) virus confirmed in Zhejiang province.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the three waves of avian influenza A(H7N9) virus circulation since live poultry markets were permanently closed in the main urban areas in Zhejiang Province, July 2014‐June 2017

Cheng

Wang

Shen

et al. 2018

Influenza Resp Viruses

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BackgroundThe sudden increase in the number of human cases infected with avian influenza A(H7N9) virus after September 2016 raised global concern.ObjectivesTo assess the changes in epidemiological characteristics of H7N9 cases since the massive closure of live poultry markets (LPMs) in the main urban areas in Zhejiang province.MethodsWe used descriptive statistics to compare epidemiological characteristics of the three distinct waves of H7N9 cases in Zhejiang province. The rural or urban cases were defined according to the location where the patients had exposure within 2 weeks before illness onset.ResultsBetween July 2014 and June 2017, 166 H7N9 cases were reported in Zhejiang province, with 45, 34, and 87 cases reported in the third, fourth, and fifth wave, respectively. Across the three waves, most reported cases were from rural areas. A similar percentage of cases in all three waves reported exposure to LPMs, raising poultry at home or around the house, as well as occupational exposure. Compared to the third (80.00%) and fourth wave (70.59%), a significantly larger proportion of cases from the non‐LPMs closure areas were observed in the fifth wave (89.66%) (P = .034).ConclusionEpidemiological characteristics of human cases infected with avian influenza A(H7N9) virus had generally remained unchanged since the massive closure of LPMs in the main urban area of Zhejiang province. The sudden increase in the number of H7N9 cases in the fifth wave was mainly attributed to the excessive cases reported from areas where LPMs were not permanently closed.

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Biological characterisation of the emerged highly pathogenic avian influenza (HPAI) A(H7N9) viruses in humans, in mainland China, 2016 to 2017

Cited by 109 publications

References 10 publications

A Highly Pathogenic Avian H7N9 Influenza Virus Isolated from A Human Is Lethal in Some Ferrets Infected via Respiratory Droplets

A Highly Pathogenic Avian H7N9 Influenza Virus Isolated from A Human Is Lethal in Some Ferrets Infected via Respiratory Droplets

Comparison of the Efficacy of N9 Neuraminidase-Specific Monoclonal Antibodies against Influenza A(H7N9) Virus Infection

Comparison of the three waves of avian influenza A(H7N9) virus circulation since live poultry markets were permanently closed in the main urban areas in Zhejiang Province, July 2014‐June 2017

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