Testing the Effect of Internal Genes Derived from a Wild-Bird-Origin H9N2 Influenza A Virus on the Pathogenicity of an A/H7N9 Virus

Su, Wen; Wang, Chengmin; Luo, Jing; Zhao, Yuliang; Wu, Yan; Chen, Lin; Zhao, Na; Li, Meng; Xing, Chao; Liu, Huimin; Zhang, Hong; Chang, Yung-Fu; Li, Tianxian; Ding, Hua; Wan, Xiu‐Feng; He, Hongxuan

doi:10.1016/j.celrep.2015.08.029

Cited by 14 publications

(18 citation statements)

References 40 publications

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“…Recent cases (2013) of avian-to-human transmission of avian influenza A virus subtypes included H7N9, H6N1, and H10N8 6, 7, 8. The case-fatality rate in over 600 cases of H7N9 infections was ∼30% 1, 9. Most recently, the World Health Organization reported another 120 cases since September 2016 resulting in 37 deaths 10 .…”

Section: Introductionmentioning

confidence: 99%

Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses

Bahl¹,

Senn

Yuzhakov³

et al. 2017

Molecular Therapy

565

482

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Recently, the World Health Organization confirmed 120 new human cases of avian H7N9 influenza in China resulting in 37 deaths, highlighting the concern for a potential pandemic and the need for an effective, safe, and high-speed vaccine production platform. Production speed and scale of mRNA-based vaccines make them ideally suited to impede potential pandemic threats. Here we show that lipid nanoparticle (LNP)-formulated, modified mRNA vaccines, encoding hemagglutinin (HA) proteins of H10N8 (A/Jiangxi-Donghu/346/2013) or H7N9 (A/Anhui/1/2013), generated rapid and robust immune responses in mice, ferrets, and nonhuman primates, as measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays. A single dose of H7N9 mRNA protected mice from a lethal challenge and reduced lung viral titers in ferrets. Interim results from a first-in-human, escalating-dose, phase 1 H10N8 study show very high seroconversion rates, demonstrating robust prophylactic immunity in humans. Adverse events (AEs) were mild or moderate with only a few severe and no serious events. These data show that LNP-formulated, modified mRNA vaccines can induce protective immunogenicity with acceptable tolerability profiles.

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Section: Introductionmentioning

confidence: 99%

Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses

Bahl¹,

Senn

Yuzhakov³

et al. 2017

Molecular Therapy

565

482

View full text Add to dashboard Cite

show abstract

“…Of the H9N2-like PB1s, 18 isolates contained a full length PB1-F2 (90aa), 5 had a minor truncation (76aa), and a single isolate had a major truncation (27aa). 76aa long PB1-F2s from H9N2 viruses has previously been implied to increase the virulence of H7N9 viruses in mice but are thought not to interfere with function ( Gibbs et al, 2003 , Su et al, 2015 ). PB1-F2 functional knockouts, similar to the 27aa variant seen, have also been shown to increase virulence of avian influenza viruses ( Gibbs et al, 2003 ).…”

Section: Resultsmentioning

confidence: 99%

Prevalence and diversity of H9N2 avian influenza in chickens of Northern Vietnam, 2014

Thuy

Peacock

Bich

et al. 2016

Infection, Genetics and Evolution

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Despite their classification as low pathogenicity avian influenza viruses (LPAIV), A/H9N2 viruses cause significant losses in poultry in many countries throughout Asia, the Middle East and North Africa. To date, poultry surveillance in Vietnam has focused on detection of influenza H5 viruses, and there is limited understanding of influenza H9 epidemiology and transmission dynamics. We determined prevalence and diversity of influenza A viruses in chickens from live bird markets (LBM) of 7 northern Vietnamese provinces, using pooled oropharyngeal swabs collected from October to December 2014. Screening by real time RT-PCR revealed 1207/4900 (24.6%) of pooled swabs to be influenza A virus positive; overall prevalence estimates after accounting for pooling (5 swabs/pools) were 5.8% (CI 5.4–6.0). Subtyping was performed on 468 pooled swabs with M gene Ct < 26. No influenza H7 was detected; 422 (90.1%) were H9 positive; and 22 (4.7%) were H5 positive. There was no evidence was of interaction between H9 and H5 virus detection rates. We sequenced 17 whole genomes of A/H9N2, 2 of A/H5N6, and 11 partial genomes. All H9N2 viruses had internal genes that clustered with genotype 57 and were closely related to Chinese human isolates of A/H7N9 and A/H10N8. Using a nucleotide divergence cutoff of 98%, we identified 9 distinct H9 genotypes. Phylogenetic analysis suggested multiple introductions of H9 viruses to northern Vietnam rather than in-situ transmission. Further investigations of H9 prevalence and diversity in other regions of Vietnam are warranted to assess H9 endemicity elsewhere in the country.

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“…In our previous studies, we showed that diverse wild bird H9N9 influenza virus genes elevated the virulence of a H7N9 virus (Su et al, 2015). Recently, cases of human infections with newly reasserted influenza A (H7N9) virus have been continuously reported in China (Sha et al, 2016; Shen and Lu, 2017).…”

Section: Discussionmentioning

confidence: 99%

Amino Acid Substitution K470R in the Nucleoprotein Increases the Virulence of H5N1 Influenza A Virus in Mammals

et al. 2017

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H5N1 is a highly pathogenic influenza A virus (IAV) and poses a major threat to the public health. The nucleoprotein (NP) has a multiple functions during the viral life cycle, however, the precise role of NP mutants in viral replication and pathogenicity is not completely understood. Here, we attempted to identify five residues in NP that may contribute to viral replication or pathogenicity. Of these, K227R, K229R, and K470R viruses were successfully rescued by reverse genetic, but the K91R and K198R viruses were not viable. A mini-genome assay demonstrated that the NP mutations K91R and K198R significantly decreased the polymerase activity. Moreover, these two mutations resulted in disrupted cellular localization in mammalian cells. Importantly, mutation at position 470 of NP significantly increased its virulence in vitro and in vivo. These findings demonstrated that the NP protein plays a major role in influenza virulence and pathogenicity, which adds to the knowledge of IAV virulence determinants and may benefit IAV surveillance.

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Testing the Effect of Internal Genes Derived from a Wild-Bird-Origin H9N2 Influenza A Virus on the Pathogenicity of an A/H7N9 Virus

Cited by 14 publications

References 40 publications

Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses

Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses

Prevalence and diversity of H9N2 avian influenza in chickens of Northern Vietnam, 2014

Amino Acid Substitution K470R in the Nucleoprotein Increases the Virulence of H5N1 Influenza A Virus in Mammals

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