scholarly journals Molecular evolution, diversity and adaptation of H7N9 influenza A viruses in China

2017 ◽  
Author(s):  
Jing Lu ◽  
Jayna Raghwani ◽  
Jie Wu ◽  
Rhys Pryce ◽  
Thomas A. Bowden ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Influenza A ◽  
Phylogenetic Analyses ◽  
High Rate ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Receptor Recognition ◽  
Sequence Reconstruction ◽  
Current Outbreak ◽  
H7n9 Influenza

SummaryA novel H7N9 avian influenza virus has caused five human epidemics in China since 2013. The substantial increase in prevalence and the emergence of antigenically divergent or highly pathogenic (HP) H7N9 strains during the current outbreak raises concerns about the epizootic-potential of these viruses. Here, we investigate the evolution and adaptation of H7N9 by combining publicly available data with newly generated virus sequences isolated in Guangdong between 2015-2017. Phylogenetic analyses show that currently-circulating H7N9 viruses belong to distinct lineages with differing spatial distributions. Using ancestral sequence reconstruction and structural modelling we have identified parallel amino-acid changes on multiple separate lineages. Furthermore, we infer mutations in HA primarily occur at sites involved in receptor-recognition and/or antigenicity. We also identify seven new HP strains, which likely emerged from viruses circulating in eastern Guangdong around March 2016 and is further associated with a high rate of adaptive molecular evolution.

scholarly journals Parallel Evolution in the Emergence of Highly Pathogenic Avian Influenza A Viruses

2018 ◽  
Author(s):  
Marina Escalera-Zamudio ◽  
Michael Golden ◽  
Bernardo Gutiérrez ◽  
Julien Thézé ◽  
Jeremy Russell Keown ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Avian Influenza ◽  
Protein Function ◽  
Influenza A ◽  
Parallel Evolution ◽  
Influenza Viruses ◽  
Cleavage Sites ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Virulence Evolution

ABSTRACTParallel molecular evolution and adaptation are important phenomena commonly observed in viruses. Here we exploit parallel molecular evolution to understand virulence evolution in avian influenza viruses (AIV). Highly-pathogenic AIVs independently evolve from low-pathogenic ancestors via acquisition of a polybasic cleavage sites (pCS). Why some AIV lineages but not others evolve in this way is unknown. We hypothesise that the parallel emergence of highly-pathogenic AIV may be facilitated by permissive or compensatory mutations occurring across the AIV genome. We combined phylogenetic, statistical and structural approaches to discover parallel mutations in AIV genomes associated with the highly-pathogenic phenotype. Parallel mutations were screened using a new statistical test of mutation-phenotype association and further evaluated in the contexts of positive selection and protein function. The mutational panel we present reveals new links between virulence evolution and other viral traits and raises the possibility of predicting aspects of AIV evolution.

scholarly journals Parallel evolution in the emergence of highly pathogenic avian influenza A viruses

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Marina Escalera-Zamudio ◽  
Michael Golden ◽  
Bernardo Gutiérrez ◽  
Julien Thézé ◽  
Jeremy Russell Keown ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Avian Influenza ◽  
Influenza A ◽  
Parallel Evolution ◽  
Influenza Viruses ◽  
Cleavage Sites ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Virulence Evolution ◽  
Compensatory Mutations

AbstractParallel molecular evolution and adaptation are important phenomena commonly observed in viruses. Here, we exploit parallel molecular evolution to understand virulence evolution in avian influenza viruses (AIV). Highly-pathogenic AIVs evolve independently from low-pathogenic ancestors via acquisition of polybasic cleavage sites. Why some AIV lineages but not others evolve in this way is unknown. We hypothesise that the parallel emergence of highly-pathogenic AIV may be facilitated by permissive or compensatory mutations occurring across the viral genome. We combine phylogenetic, statistical and structural approaches to discover parallel mutations in AIV genomes associated with the highly-pathogenic phenotype. Parallel mutations were screened using a statistical test of mutation-phenotype association and further evaluated in the contexts of positive selection and protein structure. Our resulting mutational panel may help to reveal new links between virulence evolution and other traits, and raises the possibility of predicting aspects of AIV evolution.

scholarly journals Treatment of Highly Pathogenic H7N9 Virus-Infected Mice with Baloxavir Marboxil

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1066 ◽  
Author(s):  
Maki Kiso ◽  
Seiya Yamayoshi ◽  
Yuri Furusawa ◽  
Masaki Imai ◽  
Yoshihiro Kawaoka
Keyword(s):  
Virus Infection ◽  
Influenza A ◽  
H7n9 Virus ◽  
Neuraminidase Inhibitors ◽  
Influenza A Viruses ◽  
Lethal Challenge ◽  
Highly Pathogenic ◽  
Limited Efficacy ◽  
H7n9 Influenza ◽  
Influenza H7n9 Virus

Viral neuraminidase inhibitors show limited efficacy in mice infected with H7N9 influenza A viruses isolated from humans. Although baloxavir marboxil protected mice from lethal challenge infection with a low pathogenic avian influenza H7N9 virus isolated from a human, its efficacy in mice infected with a recent highly pathogenic version of H7N9 human isolates is unknown. Here, we examined the efficacy of baloxavir marboxil in mice infected with a highly pathogenic human H7N9 virus, A/Guangdong/17SF003/2016. Treatment of infected mice with a single 1.5 mg/kg dose of baloxavir marboxil protected mice from the highly pathogenic human H7N9 virus infection as effectively as oseltamivir treatment at 50 mg/kg twice a day for five days. Daily treatment for five days at 15 or 50 mg/kg of baloxavir marboxil showed superior therapeutic efficacy, largely preventing virus replication in respiratory organs. These results indicate that baloxavir marboxil is a valuable candidate treatment for human patients suffering from highly pathogenic H7N9 virus infection.

Highly Pathogenic H5N1 and Novel H7N9 Influenza A Viruses Induce More Profound Proteomic Host Responses than Seasonal and Pandemic H1N1 Strains

2015 ◽  
Vol 14 (11) ◽  
pp. 4511-4523 ◽  
Author(s):  
Philippe François Simon ◽  
Stuart McCorrister ◽  
Pingzhao Hu ◽  
Patrick Chong ◽  
Alex Silaghi ◽  
...  
Keyword(s):  
Influenza A ◽  
Host Responses ◽  
Pandemic H1n1 ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
H7n9 Influenza ◽  
Pathogenic H5n1

scholarly journals Plasticity of the Influenza Virus H5 HA Protein

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huihui Kong ◽  
David F. Burke ◽  
Tiago Jose da Silva Lopes ◽  
Kosuke Takada ◽  
Masaki Imai ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Mammalian Cells ◽  
Influenza A ◽  
Viral Antigen ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Antigenic Properties ◽  
Ha Protein

ABSTRACT Since the emergence of highly pathogenic avian influenza viruses of the H5 subtype, the major viral antigen, hemagglutinin (HA), has undergone constant evolution, resulting in numerous genetic and antigenic (sub)clades. To explore the consequences of amino acid changes at sites that may affect the antigenicity of H5 viruses, we simultaneously mutated 17 amino acid positions of an H5 HA by using a synthetic gene library that, theoretically, encodes all combinations of the 20 amino acids at the 17 positions. All 251 mutant viruses sequenced possessed ≥13 amino acid substitutions in HA, demonstrating that the targeted sites can accommodate a substantial number of mutations. Selection with ferret sera raised against H5 viruses of different clades resulted in the isolation of 39 genotypes. Further analysis of seven variants demonstrated that they were antigenically different from the parental virus and replicated efficiently in mammalian cells. Our data demonstrate the substantial plasticity of the influenza virus H5 HA protein, which may lead to novel antigenic variants. IMPORTANCE The HA protein of influenza A viruses is the major viral antigen. In this study, we simultaneously introduced mutations at 17 amino acid positions of an H5 HA expected to affect antigenicity. Viruses with ≥13 amino acid changes in HA were viable, and some had altered antigenic properties. H5 HA can therefore accommodate many mutations in regions that affect antigenicity. The substantial plasticity of H5 HA may facilitate the emergence of novel antigenic variants.

Experimental infection of ostriches with H7N1 low pathogenic and H5N8 clade 2.3.4.4B highly pathogenic influenza A viruses

2021 ◽  
pp. 109251
Author(s):  
Celia Abolnik ◽  
Erich Ostmann ◽  
Matthew Woods ◽  
Daniel B.R. Wandrag ◽  
John Grewar ◽  
...  
Keyword(s):  
Experimental Infection ◽  
Influenza A ◽  
Influenza A Viruses ◽  
Highly Pathogenic

scholarly journals An Avian H7N1 Gain-of-Function Experiment of Great Concern

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Simon Wain-Hobson
Keyword(s):  
Influenza A ◽  
Case Fatality ◽  
Influenza A Viruses ◽  
Gain Of Function ◽  
Highly Pathogenic ◽  
Dead End ◽  
Spanish Flu ◽  
Potential Risks ◽  
Novel Virus ◽  
H7n1 Virus

ABSTRACT Inappropriately named gain-of-function influenza research seeks to confer airborne transmission on avian influenza A viruses that otherwise cause only dead-end infections in humans. A recent study has succeeded in doing this with a highly pathogenic ostrich H7N1 virus in a ferret model without loss of virulence. If transposable to humans, this would constitute a novel virus with a case fatality rate ~30 greater than that of Spanish flu. A commentary from three distinguished virologists considered the benefits of this work to outweigh potential risks. I beg to disagree with conclusions in both papers, for the underlying science is not as strong as it appears.

scholarly journals A28 Spatial spread of highly pathogenic avian influenza A (H5N8) virus in Italy, 2017–8

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
B Zecchin ◽  
A Fusaro ◽  
G Zamperin ◽  
A Milani ◽  
A Schivo ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Spatial Information ◽  
Highly Pathogenic Avian Influenza ◽  
Phylogenetic Analyses ◽  
Illumina Miseq ◽  
Highly Pathogenic ◽  
Wild Duck ◽  
Pathogenic Avian Influenza ◽  
Domestic Birds

Abstract In winter 2016–7 the highly pathogenic avian influenza (HPAI) virus, H5N8 subtype, clade 2.3.4.4 group B, circulated extensively both in wild and domestic birds in Europe. Northern Italy was hit by three epidemic waves: the first in January–May 2017, the second in July–December 2017, and the latest in March 2018. To genetically characterize the viruses circulating in Italy we used the Illumina MiSeq platform to sequence the complete genome of representative viruses from each infected farm, for a total of 86 cases in poultry and 17 in wild birds. Maximum likelihood phylogenetic analyses performed using PhyML version 3.1 identified multiple viral introductions of distinct genotypes of HPAI H5N8 viruses in Italy at the beginning of the epidemic (January–February 2017). During the second epidemic wave a single genetic group originating from the virus A/wild duck/Poland/82A/2016 seemed to have been selected, further evolving into two different clusters, namely Italy-A and Italy-B. We identified four clusters of secondary outbreaks, the largest being the epidemic in the province of Brescia between October 2017 and March 2018, which had affected 26 farms. Evolutionary and phylogeographic analyses performed with the BEAST v1.8.4 package (applying a Bayesian Markov chain Monte Carlo approach, using a constant size coalescent tree prior and a SRD06 model of nucleotide substitution) indicated that different viral introductions had probably occurred through migratory birds from West Russia, Siberia, Central and East Europe. The discrete and continuous phylogeographic analyses showed that group Italy-A had probably emerged between February and April 2017 in the province of Mantua and had then spread eastwards, circulating in the Veneto region and eastern Lombardy; on the contrary, Italy-B had arisen between March and July 2017 in the central part of Lombardy and had spread westwards, circulating in the western part of Lombardy, Emilia Romagna, and Piedmont regions. This study was instrumental to reconstruct the virus dissemination routes and indicated that wild and domestic birds from Lombardy most likely represented the key source for the re-emergence and spread of the HPAI virus during the second and the third epidemic waves. This key spatial information will help to define appropriate disease control strategies.

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