ArticleJournal of virology2019
Hemagglutinin Cleavability, Acid Stability, and Temperature Dependence Optimize Influenza B Virus for Replication in Human Airways.
Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 60 citations in OpenAlex.
- Core Warming of Coronavirus Disease 2019 Patients Undergoing Mechanical Ventilation: A Pilot Study.Therapeutic hypothermia and temperature management · 2023Trial
- Palmitoylation of glycoproteins under low temperature enhances SVCV replication.PLoS pathogens · 2026Article
- New determinant of influenza hemagglutinin cleavability identified through random mutagenesis for acid-stabilizing mutations.Microbiology spectrum · 2026Article
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
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- Characterization of the glycoproteins of fish and amphibian influenza B-like viruses.Science advances · 2025Article
- Trypstatin as a Novel TMPRSS2 Inhibitor with Broad-Spectrum Efficacy against Corona and Influenza Viruses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- From N-0385 to N-0920: Unveiling a Host-Directed Protease Inhibitor with Picomolar Antiviral Efficacy against Prevalent SARS-CoV-2 Variants.Journal of medicinal chemistry · 2025Article
- Influenza B viruses are more susceptible to high temperatures than influenza A viruses.Npj viruses · 2024Article
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- Engineering a cleaved, prefusion-stabilized influenza B virus hemagglutinin by identification and locking of all six pH switches.PNAS nexus · 2024Article
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- ACE2 acts as a novel regulator of TMPRSS2-catalyzed proteolytic activation of influenza A virus in airway cells.Journal of virology · 2024Article
- Exosome-mediated regulation of inflammatory pathway during respiratory viral disease.Virology journal · 2024Review
- Deep mutational scanning reveals the functional constraints and evolutionary potential of the influenza A virus PB1 protein.Journal of virology · 2023Article
- Existing Evidence for Influenza B Virus Adaptations to Drive Replication in Humans as the Primary Host.Viruses · 2023Review
- Expression of TMPRSS2 is up-regulated by bacterial flagellin, LPS, and Pam3Cys in human airway cells.Life science alliance · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Influenza A virus (IAV) and influenza B virus (IBV) cause yearly epidemics with significant morbidity and mortality. When zoonotic IAVs enter the human population, the viral hemagglutinin (HA) requires adaptation to achieve sustained virus transmission. In contrast, IBV has been circulating in humans, its only host, for a long period of time. Whether this entailed adaptation of IBV HA to the human airways is unknown. To address this question, we compared two seasonal IAVs (A/H1N1 and A/H3N2) and two IBVs (B/Victoria and B/Yamagata lineages) with regard to host-dependent activity of HA as the mediator of membrane fusion during viral entry. We first investigated proteolytic activation of HA by covering all type II transmembrane serine protease (TTSP) and kallikrein enzymes, many of which proved to be present in human respiratory epithelium. The IBV HA0 precursor is cleaved by a broader panel of TTSPs and activated with much higher efficiency than IAV HA0. Accordingly, knockdown of a single protease, TMPRSS2, abrogated spread of IAV but not IBV in human respiratory epithelial cells. Second, the HA fusion pH values proved similar for IBV and human-adapted IAVs (with one exception being the HA of 1918 IAV). Third, IBV HA exhibited higher expression at 33°C, a temperature required for membrane fusion by B/Victoria HA. This indicates pronounced adaptation of IBV HA to the mildly acidic pH and cooler temperature of human upper airways. These distinct and intrinsic features of IBV HA are compatible with extensive host adaptation during prolonged circulation of this respiratory virus in the human population.
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Registered trials
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.