ArticleJournal of virology2019
Cholesterol Binding to the Transmembrane Region of a Group 2 Hemagglutinin (HA) of Influenza Virus Is Essential for Virus Replication, Affecting both Virus Assembly and HA Fusion Activity.
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 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 37 citations in OpenAlex.
- Effects of Membrane Cholesterol on the Structure and Function of Selected Class A GPCRs─Challenges and Future Perspectives.Biochemistry · 2025Review
- Influenza virus infection reprograms cholesterol biosynthesis to facilitate virus replication by the TAK1-RORγ axis.PLoS pathogens · 2025Article
- Unraveling dual fusion mechanisms in BmNPV GP64: critical roles of CARC motifs and signal peptide retention.Journal of virology · 2025Article
- Cholesterol in viral envelope determines infectivity of SARS-CoV-2 and other coronaviruses.Frontiers in microbiology · 2025Article
- Review
- Molecular Dynamics Investigation of the Influenza Hemagglutinin Conformational Changes in Acidic pH.The journal of physical chemistry. B · 2024Article
- Influenza A virus infection activates STAT3 to enhance SREBP2 expression, cholesterol biosynthesis, and virus replication.iScience · 2024Article
- Cholesterol-rich lysosomes induced by respiratory syncytial virus promote viral replication by blocking autophagy flux.Nature communications · 2024Article
- Adsorption of pulmonary and exogeneous surfactants on SARS-CoV-2 spike protein.Journal of colloid and interface science · 2023Article
- Zika virus prM protein contains cholesterol binding motifs required for virus entry and assembly.Nature communications · 2023Article
- A novelMicrobiology spectrum · 2023Article
- Viral Membrane Fusion: A Dance Between Proteins and Lipids.Annual review of virology · 2023Review
- Purification and characterization of the Lassa virus transmembrane domain.Biochemistry and biophysics reports · 2023Article
- Structure of infective Getah virus at 2.8 Å resolution determined by cryo-electron microscopy.Cell discovery · 2022Article
- Review
- Hydrophobic Mismatch Controls the Mode of Membrane-Mediated Interactions of Transmembrane Peptides.Membranes · 2022Article
- Coronavirus Infection and Cholesterol Metabolism.Frontiers in immunology · 2022Review
- Drugs for the prevention and treatment of COVID-19 and its complications: An update on what we learned in the past 2 years.Frontiers in pharmacology · 2022Review
- Surfactants - Compounds for inactivation of SARS-CoV-2 and other enveloped viruses.Current opinion in colloid & interface science · 2021Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hemagglutinin (HA) of influenza virus is incorporated into cholesterol-enriched nanodomains of the plasma membrane. Phylogenetic group 2 HAs contain the conserved cholesterol consensus motif (CCM) YKLW in the transmembrane region. We previously reported that mutations in the CCM retarded intracellular transport of HA and decreased its nanodomain association. Here, we analyzed whether cholesterol interacts with the CCM. Incorporation of photocholesterol into HA was significantly reduced if the whole CCM is replaced by alanine, both using immunoprecipitated HA and when HA is embedded in the membrane. We next used reverse genetics to investigate the significance of the CCM for virus replication. No virus was rescued if the whole motif is exchanged (YKLW4A); singly (LA) or doubly (YK2A and LW2A) mutated virus showed decreased titers and a comparative fitness disadvantage. In polarized cells, transport of HA mutants to the apical membrane was not disturbed. Reduced amounts of HA and cholesterol were incorporated into the viral membrane. Mutant viruses exhibit a decrease in hemolysis, which is only partially corrected if the membrane is replenished with cholesterol. More specifically, viruses have a defect in hemifusion, as demonstrated by fluorescence dequenching. Cells expressing HA YKLW4A fuse with erythrocytes, but the number of events is reduced. Even after acidification unfused erythrocytes remain cell bound, a phenomenon not observed with wild-type HA. We conclude that cholesterol binding to a group 2 HA is essential for virus replication. It has pleiotropic effects on virus assembly and membrane fusion, mainly on lipid mixing and possibly a preceding step.
Indexed as
Identifiers
What OpenQuestion holds
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.