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H9N2 virus-derived M1 protein promotes H5N6 virus release in mammalian cells: Mechanism of avian influenza virus inter-species infection in humans
- Source :
- PLoS Pathogens, Vol 17, Iss 12, p e1010098 (2021), PLoS Pathogens
- Publication Year :
- 2021
- Publisher :
- Public Library of Science, 2021.
-
Abstract
- H5N6 highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4 not only exhibits unprecedented intercontinental spread in poultry, but can also cause serious infection in humans, posing a public health threat. Phylogenetic analyses show that 40% (8/20) of H5N6 viruses that infected humans carried H9N2 virus-derived internal genes. However, the precise contribution of H9N2 virus-derived internal genes to H5N6 virus infection in humans is unclear. Here, we report on the functional contribution of the H9N2 virus-derived matrix protein 1 (M1) to enhanced H5N6 virus replication capacity in mammalian cells. Unlike H5N1 virus-derived M1 protein, H9N2 virus-derived M1 protein showed high binding affinity for H5N6 hemagglutinin (HA) protein and increased viral progeny particle release in different mammalian cell lines. Human host factor, G protein subunit beta 1 (GNB1), exhibited strong binding to H9N2 virus-derived M1 protein to facilitate M1 transport to budding sites at the cell membrane. GNB1 knockdown inhibited the interaction between H9N2 virus-derived M1 and HA protein, and reduced influenza virus-like particles (VLPs) release. Our findings indicate that H9N2 virus-derived M1 protein promotes avian H5N6 influenza virus release from mammalian, in particular human cells, which could be a major viral factor for H5N6 virus cross-species infection.<br />Author summary H9N2 avian influenza viruses (AIVs), through reassortment of their internal genes with other circulating AIVs subtypes (H5N6, H7N9, H10N8 and H10N3 viruses), are known to enable the resulting novel reassortants to infect humans. However, the precise roles of H9N2 virus-derived internal genes in human infection remain unknown. Here, we found that H9N2 virus-derived (but not H5N1 virus-derived) M1 protein showed strong interaction with host GNB1 protein to enhance M1 protein transport to budding sites at the cell membrane to promote progeny virus release, hence facilitating H5N6 reassortants to infect human cells.
- Subjects :
- RNA viruses
Influenza Viruses
Physiology
viruses
Cell Membranes
M1 protein
Pathology and Laboratory Medicine
medicine.disease_cause
Biochemistry
Viral Zoonoses
Immune Physiology
Medicine and Health Sciences
Influenza A Virus, H9N2 Subtype
Biology (General)
Virus Release
Immune System Proteins
biology
virus diseases
Precipitation Techniques
Medical Microbiology
Influenza A virus
Viral Pathogens
Viruses
Cellular Structures and Organelles
Pathogens
GNB1
Reassortant Viruses
Research Article
QH301-705.5
Immunology
Hemagglutinin (influenza)
Transfection
Research and Analysis Methods
Microbiology
Antibodies
Virus
Viral Matrix Proteins
Virology
Influenza, Human
medicine
Genetics
Immunoprecipitation
Animals
Humans
Protein Interactions
Molecular Biology Techniques
Microbial Pathogens
Molecular Biology
Viral matrix protein
Organisms
Biology and Life Sciences
Membrane Proteins
Proteins
Cell Biology
RC581-607
Viral Replication
Influenza A virus subtype H5N1
Viral replication
Influenza in Birds
biology.protein
Parasitology
Immunologic diseases. Allergy
Chickens
Orthomyxoviruses
Subjects
Details
- Language :
- English
- ISSN :
- 15537366 and 15537374
- Database :
- OpenAIRE
- Journal :
- PLoS Pathogens, Vol 17, Iss 12, p e1010098 (2021), PLoS Pathogens
- Accession number :
- edsair.doi.dedup.....2d0e6cecb2f820564ff342fc839e9003