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Literature detail

PB2 mutations arising during H9N2 influenza evolution in the Middle East confer enhanced replication and growth in mammals.

Yasuha Arai1 Norihito Kawashita2,3 Madiha Salah Ibrahim4 Emad Mohamed Elgendy4 Tomo Daidoji1 Takao Ono5 Tatsuya Takagi3 Takaaki Nakaya1 Kazuhiko Matsumoto5 Yohei Watanabe1
Affiliations 5 institutions
  1. Department of Infectious Diseases, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  2. Faculty of Science and Engineering, Kindai University, Osaka, Japan.
  3. Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
  4. Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt.
  5. The Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.
PMID 31265471 2019 PLoS Pathog eng epublish
PubMed DOI Browse context

Article

Publication summary

Avian influenza virus H9N2 has been endemic in birds in the Middle East, in particular in Egypt with multiple cases of human infections since 1998. Despite concerns about the pandemic threat posed by H9N2, little is known about the biological properties of H9N2 in this epicentre of infection. Here, we investigated the evolutionary dynamics of H9N2 in the Middle East and identified phylogeny-associated PB2 mutations that acted cooperatively to increase H9N2 replication/transcription in human cells. The accumulation of PB2 mutations also correlated with an increase in H9N2 virus growth in the upper and lower airways of mice and in virulence. These mutations clustered on a solvent-exposed region in the PB2-627 domain in proximity to potential interfaces with host factors. These PB2 mutations have been found at high prevalence during evolution of H9N2 in the field, indicating that they have provided a selective advantage for viral adaptation to infect poultry. Therefore, continuous prevalence of H9N2 virus in the Middle East has generated a far more fit or optimized replication phenotype, leading to an expanded viral host range, including to mammals, which may pose public health risks beyond the current outbreaks.

Mutation Animals Evolution, Molecular Female HEK293 Cells Host Specificity Humans Influenza A Virus, H9N2 Subtype Influenza, Human Mammals Mice Mice, Inbred BALB C Middle East Models, Molecular Orthomyxoviridae Infections Phylogeny Reassortant Viruses RNA-Dependent RNA Polymerase

Structured evidence records

Evidence records

4 total
Host Range Experiment 2 records
Host Range Experiment Extraction confidence 0.90
Key finding

PB2 mutations enhanced replication and growth of H9N2 influenza virus in human cells and mice, demonstrating increased mammalian host adaptation.

Virus
IAV H9N2
Location
Not specified
Supporting text

PB2 mutations acted cooperatively to increase H9N2 replication/transcription in human cells. The accumulation of PB2 mutations also correlated with an increase in H9N2 virus growth in the upper and lower airways of mice and in virulence.

Method
replication assay; transcription assay
Experimental system
in vitro cell culture
Host Range Experiment Extraction confidence 0.90
Key finding

PB2 mutations led to increased growth of H9N2 virus in the respiratory tract of mice, indicating enhanced replication capacity in mammalian hosts.

Virus
IAV H9N2
Location
Not specified
Supporting text

The accumulation of PB2 mutations also correlated with an increase in H9N2 virus growth in the upper and lower airways of mice and in virulence.

Method
experimental infection; virus growth measurement
Sample type
upper airways; lower airways
Experimental system
in vivo animal experiment
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.95
Key finding

Phylogenetic analysis revealed PB2 mutations in H9N2 influenza viruses circulating in the Middle East that arose during viral evolution and enhanced viral replication in mammals, indicating host range expansion.

Virus
IAV H9N2
Host
Mammalia
Location
Not specified
Supporting text

We investigated the evolutionary dynamics of H9N2 in the Middle East and identified phylogeny-associated PB2 mutations that acted cooperatively to increase H9N2 replication/transcription in human cells. These PB2 mutations have been found at high prevalence during evolution of H9N2 in the field, indicating selective advantage for adaptation to infect poultry and mammals.

Genes or proteins
PB2
Analysis methods
phylogenetic analysis; evolutionary dynamics analysis
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 1.00
Key finding

PB2 mutations in H9N2 influenza virus enhance replication and transcription in human cells and increase growth and virulence in mice, signifying adaptive molecular changes facilitating infection in mammals.

Virus
IAV H9N2
Host
Not specified
Location
Not specified
Supporting text

We identified phylogeny-associated PB2 mutations that acted cooperatively to increase H9N2 replication/transcription in human cells. The accumulation of PB2 mutations also correlated with an increase in H9N2 virus growth in the upper and lower airways of mice and in virulence.

Genes or proteins
PB2
Mechanism types
replication_efficiency; pathogenicity; host_factor_interaction