Literature detail

Full factorial analysis of mammalian and avian influenza polymerase subunits suggests a role of an efficient polymerase for virus adaptation.

Olive T W Li¹ Michael C W Chan Cynthia S W Leung Renee W Y Chan Yi Guan John M Nicholls Leo L M Poon

Affiliations 1 institutions

State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China.

PMID 19462010 2009 PLoS One eng epublish

Article

Publication summary

Amongst all the internal gene segments (PB2. PB1, PA, NP, M and NS), the avian PB1 segment is the only one which was reassorted into the human H2N2 and H3N2 pandemic strains. This suggests that the reassortment of polymerase subunit genes between mammalian and avian influenza viruses might play roles for interspecies transmission. To test this hypothesis, we tested the compatibility between PB2, PB1, PA and NP derived from a H5N1 virus and a mammalian H1N1 virus. All 16 possible combinations of avian-mammalian chimeric viral ribonucleoproteins (vRNPs) were characterized. We showed that recombinant vRNPs with a mammalian PB2 and an avian PB1 had the strongest polymerase activities in human cells at all studied temperature. In addition, viruses with this specific PB2-PB1 combination could grow efficiently in cell cultures, especially at a high incubation temperature. These viruses were potent inducers of proinflammatory cytokines and chemokines in primary human macrophages and pneumocytes. Viruses with this specific PB2-PB1 combination were also found to be more capable to generate adaptive mutations under a new selection pressure. These results suggested that the viral polymerase activity might be relevant for the genesis of influenza viruses of human health concern.

Adaptation, Biological Animals Birds Cell Line Chickens Cytokines Dogs Genes, Viral Humans Inflammation Mediators Influenza A virus Influenza in Birds Luciferases Mammals Mutation Protein Subunits RNA-Dependent RNA Polymerase Selection, Genetic

Structured evidence records

Evidence records

4 total

Cross Species Transmission 1 records

Cross Species Transmission Extraction confidence 0.85

Key finding

Reassortment experiments between avian H5N1 and mammalian H1N1 influenza viruses showed that polymerase gene combinations can enable cross-species adaptation and potentially facilitate transmission between mammalian and avian hosts.

Virus

Host

Location

Supporting text

The abstract states that 'the reassortment of polymerase subunit genes between mammalian and avian influenza viruses might play roles for interspecies transmission' and describes testing compatibility between PB2, PB1, PA and NP derived from a H5N1 virus and a mammalian H1N1 virus.

Method: reassortment analysis; polymerase activity assay
Study design: animal experiment
Transmission direction: animal-to-animal

Genomic Evolution 1 records

Genomic Evolution Extraction confidence 0.80

Key finding

Reassortment of PB2 from mammalian H1N1 and PB1 from avian H5N1 produced recombinant viral polymerases with enhanced activity in human cells, demonstrating adaptive potential linked to subunit combination.

Virus

Host

Location

Supporting text

We tested the compatibility between PB2, PB1, PA and NP derived from a H5N1 virus and a mammalian H1N1 virus. All 16 possible combinations of avian-mammalian chimeric viral ribonucleoproteins (vRNPs) were characterized. We showed that recombinant vRNPs with a mammalian PB2 and an avian PB1 had the strongest polymerase activities in human cells at all studied temperatures.

Genes or proteins: PB2; PB1; PA; NP
Analysis methods: reassortment analysis; comparative genomic analysis of polymerase subunits

Molecular Adaptation 1 records

Molecular Adaptation Extraction confidence 0.95

Key finding

A combination of mammalian PB2 and avian PB1 subunits enhanced influenza polymerase activity and viral growth in human cells, indicating polymerase-driven molecular adaptation.

Virus

Host

Location

Supporting text

We showed that recombinant vRNPs with a mammalian PB2 and an avian PB1 had the strongest polymerase activities in human cells at all studied temperature. In addition, viruses with this specific PB2-PB1 combination could grow efficiently in cell cultures, especially at a high incubation temperature.

Genes or proteins: PB2; PB1
Mechanism types: polymerase_activity; replication_efficiency

Recombination Or Reassortment 1 records

Recombination Or Reassortment Extraction confidence 0.90

Key finding

Reassortment between avian H5N1 and mammalian H1N1 influenza polymerase subunits, particularly a mammalian PB2 combined with an avian PB1, generated recombinant viruses with enhanced polymerase activity and growth in human cells, suggesting a mechanism for cross-species adaptation.

Virus

Host

Location

Supporting text

The avian PB1 segment is the only one which was reassorted into the human H2N2 and H3N2 pandemic strains. This suggests that the reassortment of polymerase subunit genes between mammalian and avian influenza viruses might play roles for interspecies transmission. ... We showed that recombinant vRNPs with a mammalian PB2 and an avian PB1 had the strongest polymerase activities in human cells.

Event type: reassortment
Genes or segments: PB2; PB1

Citation context

References

87 references

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Evidence overview

Evidence 4

Types 4

Virus 4

Host 1

Evidence types

Cross Species Transmission 1 Genomic Evolution 1 Molecular Adaptation 1 Recombination Or Reassortment 1

Linked entities

Viruses

Hosts

Locations

Publication metadata

Journal: PloS one
Volume / Issue / Pages: 4 / 5 / e5658
ISSN: 1932-6203
Journal country: United States
DOI: 10.1371/journal.pone.0005658