ArticleJournal of virology2012
A single amino acid at the hemagglutinin cleavage site contributes to the pathogenicity and neurovirulence of H5N1 influenza virus in mice.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Decoding the lung-brain axis in influenza: from pulmonary infection to central nervous system injury.Journal of neuroinflammation · 2026Review
- Reverse genetics-derived cattle H5N1 virus from Clade 2.3.4.4b shows enhanced systemic infectivity and pathogenicity than an older Clade 1 H5N1 virus in BALB/c mice.Emerging microbes & infections · 2025Article
- Molecular Evolution of the H5 and H7 Highly Pathogenic Avian Influenza Virus Haemagglutinin Cleavage Site Motif.Reviews in medical virology · 2025Review
- Avian influenza overview December 2023-March 2024.EFSA journal. European Food Safety Authority · 2024Article
- Molecular characterization and phylogenetic analysis of highly pathogenic H5N1 clade 2.3.4.4b virus in Bosnia and Herzegovina.Frontiers in veterinary science · 2023Article
- Co-existence and co-infection of influenza A viruses and coronaviruses: Public health challenges.Innovation (Cambridge (Mass.)) · 2022Review
- Effect of the Interaction between Viral PB2 and Host SphK1 on H9N2 AIV Replication in Mammals.Viruses · 2022Article
- Combined insertion of basic and non-basic amino acids at hemagglutinin cleavage site of highly pathogenic H7N9 virus promotes replication and pathogenicity in chickens and mice.Virologica Sinica · 2022Article
- Reassortant Highly Pathogenic H5N6 Avian Influenza Virus Containing Low Pathogenic Viral Genes in a Local Live Poultry Market, Vietnam.Current microbiology · 2021Article
- Differential Diagnosis for Highly Pathogenic Avian Influenza Virus Using Nanoparticles Expressing Chemiluminescence.Viruses · 2021Article
- Reassortment with dominant chicken H9N2 influenza virus contributed to the fifth H7N9 virus human epidemic.Journal of virology · 2021Article
- Neurovirulence of avian influenza virus is dependent on the interaction of viral NP protein with host factor FMRP in the murine brain.Journal of virology · 2021Article
- A risk marker of tribasic hemagglutinin cleavage site in influenza A (H9N2) virus.Communications biology · 2021Article
- Novel pathogenic characteristics of highly pathogenic avian influenza virus H7N9: viraemia and extrapulmonary infection.Emerging microbes & infections · 2020Article
- Exploring utility of genomic epidemiology to trace origins of highly pathogenic influenza A/H7N9 in Guangdong.Virus evolution · 2020Article
- Inventory of molecular markers affecting biological characteristics of avian influenza A viruses.Virus genes · 2019Review
- Article
- Prevailing I292V PB2 mutation in avian influenza H9N2 virus increases viral polymerase function and attenuates IFN-β induction in human cells.The Journal of general virology · 2019Article
- The use of pyrosequencing for detection of hemagglutinin mutations associated with increased pathogenicity of H5N1 avian influenza viruses in mammals.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2018Article
- New Threats from H7N9 Influenza Virus: Spread and Evolution of High- and Low-Pathogenicity Variants with High Genomic Diversity in Wave Five.Journal of virology · 2018Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
H5 influenza viruses containing a motif of multiple basic amino acids at the hemagglutinin (HA) cleavage site (HACS) are highly pathogenic in chicken but display different virulence phenotypes in mammals. Previous studies have shown that multiple basic amino acids of H5N1 influenza virus are a prerequisite for lethality in mice. However, it remains unclear which specific residue at the cleavage site affects the pathogenicity of H5N1 in mammals. A comprehensive genetic analysis of the H5N1 HACS showed that residues at P6 (position 325, by H3 numbering) were the most polymorphic, including serine (S), arginine (R), deletion (*), glycine (G), and isoleucine (I). To determine whether a single residue at P6 could affect virulence, we introduced different mutations at P6 of an avirulent clade 7 H5N1 strain, rg325G, by reverse genetics. Among the recombinant viruses, the rg325S virus showed the highest cleavage efficiency in vitro. All these viruses were highly pathogenic in chicken but exhibited different virulences in mice. The rg325S virus exhibited the highest pathogenicity in terms of unrestricted organ tropism and neurovirulence. Remarkably, the HA-325S substitution dramatically increased the pathogenicity of H5N1 viruses of other clades, including clades 2.2, 2.3.2, and 2.3.4, indicating that this residue impacts genetically divergent H5N1 viruses. An analysis of predicted structures containing these mutations showed that the cleavage site loop with 325S was the most exposed, which might be responsible for the efficient cleavage and high virulence. Our results demonstrate that an amino acid substitution at the P6 cleavage site alone could modulate the virulence of H5N1 in mice.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.