ArticleJournal of virology2017
pH Optimum of Hemagglutinin-Mediated Membrane Fusion Determines Sensitivity of Influenza A Viruses to the Interferon-Induced Antiviral State and IFITMs.
Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 67 citations in OpenAlex.
- New determinant of influenza hemagglutinin cleavability identified through random mutagenesis for acid-stabilizing mutations.Microbiology spectrum · 2026Article
- IFITM1 as a modulator of surfaceome dynamics and aggressive phenotype in cervical cancer cells.Oncology reports · 2025Article
- IFITM1 is a host restriction factor that inhibits porcine epidemic diarrhea virus infection.Journal of nanobiotechnology · 2024Article
- Role of Viral Envelope Proteins in Determining Susceptibility of Viruses to IFITM Proteins.Viruses · 2024Review
- The pro-inflammatory response to influenza A virus infection is fueled by endothelial cells.Life science alliance · 2023Article
- Hemagglutinin destabilization in H3N2 vaccine reference viruses skews antigenicity and prevents airborne transmission in ferrets.Science advances · 2023Article
- A protective measles virus-derived vaccine inducing long-lasting immune responses against influenza A virus H7N9.NPJ vaccines · 2023Article
- Current Opinion in LAIV: A Matter of Parent Virus Choice.International journal of molecular sciences · 2022Review
- IFITM protein regulation and functions: Far beyond the fight against viruses.Frontiers in immunology · 2022Review
- Positive Regulation of the Antiviral Activity of Interferon-Induced Transmembrane Protein 3 by S-Palmitoylation.Frontiers in immunology · 2022Review
- Effects of Receptor Specificity and Conformational Stability of Influenza A Virus Hemagglutinin on Infection and Activation of Different Cell Types in Human PBMCs.Frontiers in immunology · 2022Article
- Hemagglutinins of Avian Influenza Viruses Are Proteolytically Activated by TMPRSS2 in Human and Murine Airway Cells.Journal of virology · 2021Article
- Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.PLoS pathogens · 2021Article
- Relationship between hemagglutinin stability and influenza virus persistence after exposure to low pH or supraphysiological heating.PLoS pathogens · 2021Article
- Ferret Interferon (IFN)-Inducible Transmembrane Proteins Are Upregulated by both IFN-α and Influenza Virus Infection.Journal of virology · 2021Article
- Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model.Viruses · 2021Article
- The Polybasic Cleavage Site in SARS-CoV-2 Spike Modulates Viral Sensitivity to Type I Interferon and IFITM2.Journal of virology · 2021Article
- Article
- pH-Dependent Mechanisms of Influenza Infection Mediated by Hemagglutinin.Frontiers in molecular biosciences · 2021Review
- Endothelial Cells in Emerging Viral Infections.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The replication and pathogenicity of influenza A viruses (IAVs) critically depend on their ability to tolerate the antiviral interferon (IFN) response. To determine a potential role for the IAV hemagglutinin (HA) in viral sensitivity to IFN, we studied the restriction of IAV infection in IFN-β-treated human epithelial cells by using 2:6 recombinant IAVs that shared six gene segments of A/Puerto Rico/8/1934 virus (PR8) and contained HAs and neuraminidases of representative avian, human, and zoonotic H5N1 and H7N9 viruses. In A549 and Calu-3 cells, viruses displaying a higher pH optimum of HA-mediated membrane fusion, H5N1-PR8 and H7N9-PR8, were less sensitive to the IFN-induced antiviral state than their counterparts with HAs from duck and human viruses, which fused at a lower pH. The association between a high pH optimum of fusion and reduced IFN sensitivity was confirmed by using HA point mutants of A/Hong Kong/1/1968-PR8 that differed solely by their fusion properties. Furthermore, similar effects of the viral fusion pH on IFN sensitivity were observed in experiments with (i) primary human type II alveolar epithelial cells and differentiated cultures of human airway epithelial cells, (ii) nonrecombinant zoonotic and pandemic IAVs, and (iii) preparations of IFN-α and IFN-λ1. A higher pH of membrane fusion and reduced sensitivity to IFN correlated with lower restriction of the viruses in MDCK cells stably expressing the IFN-inducible transmembrane proteins IFITM2 and IFITM3, which are known to inhibit viral fusion. Our results reveal that the pH optimum of HA-driven membrane fusion of IAVs is a determinant of their sensitivity to IFN and IFITM proteins.
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