Regulation of Paramyxovirus Fusion Activation: the Hemagglutinin-Neuraminidase Protein Stabilizes the Fusion Protein in a Pretriggered State
| Autor: | Zuhair Salah, Long Gui, Laura M. Palermo, Matteo Porotto, Eric M. Jurgens, Anne Moscona, Christine C. Yokoyama, Kelly K. Lee, Ilaria DeVito, Hong Lu |
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| Přispěvatelé: | Porotto, Matteo, Salah, Zuhair W., Gui, Long, Devito, Ilaria, Jurgens, Eric M., Lu, Hong, Yokoyama, Christine C., Palermo, Laura M., Lee, Kelly K., Moscona, Anne |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Immunology
Hemagglutinin (influenza) Receptors Cell Surface Microbiology Cell Line chemistry.chemical_compound Virology Humans HN Protein Receptor Viral Fusion Protein biology Protein Stability Temperature Lipid bilayer fusion Virus Internalization Flow Cytometry beta-Galactosidase Molecular biology Fusion protein Sialic acid Virus-Cell Interactions Parainfluenza Virus 1 Human chemistry Microscopy Fluorescence Insect Science biology.protein Neuraminidase Hemagglutinin-neuraminidase Viral Fusion Proteins Human |
| Popis: | The hemagglutinin (HA)-neuraminidase protein (HN) of paramyxoviruses carries out three discrete activities, each of which affects the ability of HN to promote viral fusion and entry: receptor binding, receptor cleaving (neuraminidase), and triggering of the fusion protein. Binding of HN to its sialic acid receptor on a target cell triggers its activation of the fusion protein (F), which then inserts into the target cell and mediates the membrane fusion that initiates infection. We provide new evidence for a fourth function of HN: stabilization of the F protein in its pretriggered state before activation. Influenza virus hemagglutinin protein (uncleaved HA) was used as a nonspecific binding protein to tether F-expressing cells to target cells, and heat was used to activate F, indicating that the prefusion state of F can be triggered to initiate structural rearrangement and fusion by temperature. HN expression along with uncleaved HA and F enhances the F activation if HN is permitted to engage the receptor. However, if HN is prevented from engaging the receptor by the use of a small compound, temperature-induced F activation is curtailed. The results indicate that HN helps stabilize the prefusion state of F, and analysis of a stalk domain mutant HN reveals that the stalk domain of HN mediates the F-stabilization effect. |
| Databáze: | OpenAIRE |
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