ArticleScientific reports2018
Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Rule-based meta-analysis reveals the major role of PB2 in influencing influenza A virus virulence in mice.BMC genomics · 2019Pooled it
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- Decoding non-human mammalian adaptive signatures of 2.3.4.4b H5N1 to assess its human adaptive potential.Microbiology spectrum · 2025Article
- Comparative Mutational Analysis and the Glycosylation Patterns of a Peruvian Isolated Avian Influenza A Virus H5N1: Exploring Possible Viral Spillover Events Within One Health Approach.Veterinary sciences · 2025Article
- Evolutionary dynamics and molecular epidemiology of H1N1 pandemic 2009 influenza A viruses across swine farms in Denmark.Virus evolution · 2025Article
- Recurring incursions and dissemination of novel Eurasian-origin H5Nx avian influenza viruses in Atlantic Canada.Virus evolution · 2024Article
- Comparison of Clinical Features and Outcomes of Medically Attended COVID-19 and Influenza Patients in a Defined Population in the 2020 Respiratory Virus Season.Frontiers in public health · 2021Article
- PA Mutations Inherited during Viral Evolution Act Cooperatively To Increase Replication of Contemporary H5N1 Influenza Virus with an Expanded Host Range.Journal of virology · 2020Article
- H9N2 Influenza Virus Infections in Human Cells Require a Balance between Neuraminidase Sialidase Activity and Hemagglutinin Receptor Affinity.Journal of virology · 2020Article
- Genetic and antigenic characterization of influenza A/H5N1 viruses isolated from patients in Indonesia, 2008-2015.Virus genes · 2020Article
- FluConvert and IniFlu: a suite of integrated software to identify novel signatures of emerging influenza viruses with increasing risk.BMC bioinformatics · 2020Article
- Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses.Viruses · 2020Review
- The Importance of Vaccinating Children and Pregnant Women against Influenza Virus Infection.Pathogens (Basel, Switzerland) · 2019Review
- Insights into the Acquisition of Virulence of Avian Influenza Viruses during a Single Passage in Ferrets.Viruses · 2019Article
- PB2 mutations arising during H9N2 influenza evolution in the Middle East confer enhanced replication and growth in mammals.PLoS pathogens · 2019Article
- Article
- Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection.Emerging microbes & infections · 2019Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of the influenza virus polymerase complex in host range restriction has been well-studied and several host range determinants, such as the polymerase PB2-E627K and PB2-D701N mutations, have been identified. However, there may be additional, currently unknown, human adaptation polymerase mutations. Here, we used a database search of influenza virus H5N1 clade 1.1, clade 2.3.2.1 and clade 2.3.4 strains isolated from 2008-2012 in Southern China, Vietnam and Cambodia to identify polymerase adaptation mutations that had been selected in infected patients. Several of these mutations acted either alone or together to increase viral polymerase activity in human airway cells to levels similar to the PB2-D701N and PB2-E627K single mutations and to increase progeny virus yields in infected mouse lungs to levels similar to the PB2-D701N single mutation. In particular, specific mutations acted synergistically with the PB2-D701N mutation and showed synergistic effects on viral replication both in human airway cells and mice compared with the corresponding single mutations. Thus, H5N1 viruses in infected patients were able to acquire multiple polymerase mutations that acted cooperatively for human adaptation. Our findings give new insight into the human adaptation of AI viruses and help in avian influenza virus risk assessment.
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