The human metapneumovirus small hydrophobic protein has properties consistent with those of a viroporin and can modulate viral fusogenic activity
| Autor: | Carole L. Moncman, Angela G Jones, Farah El Najjar, Andres Chang, Cyril Masante, Rebecca Ellis Dutch |
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| Přispěvatelé: | Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), College of Mathematics and Computer Sciences [Fuzhou], Fuzhou University, Met Office Hadley Centre for Climate Change (MOHC), United Kingdom Met Office [Exeter] |
| Rok vydání: | 2014 |
| Předmět: |
Membrane permeability
viruses Immunology Retroviridae Proteins Oncogenic Biology Microbiology Giant Cells Permeability Cell membrane Virology Chlorocebus aethiops medicine Animals Humans Viral Regulatory and Accessory Proteins Vero Cells ComputingMilieux_MISCELLANEOUS chemistry.chemical_classification Glycosaminoglycan binding Microscopy Confocal Cell Membrane Lipid bilayer fusion virus diseases Viral membrane Virus Internalization Fusion protein Molecular biology respiratory tract diseases Virus-Cell Interactions Transmembrane domain medicine.anatomical_structure [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology chemistry Insect Science COS Cells Metapneumovirus Hygromycin B Glycoprotein Ultracentrifugation Plasmids |
| Zdroj: | Journal of Human Virology Journal of Human Virology, Lippincott Williams & Wilkins (LWW), 2014, 88, pp.6423-33 |
| ISSN: | 1098-5514 1090-9508 |
| Popis: | Human metapneumovirus (HMPV) encodes three glycoproteins: the glycoprotein, which plays a role in glycosaminoglycan binding, the fusion (F) protein, which is necessary and sufficient for both viral binding to the target cell and fusion between the cellular plasma membrane and the viral membrane, and the small hydrophobic (SH) protein, whose function is unclear. The SH protein of the closely related respiratory syncytial virus has been suggested to function as a viroporin, as it forms oligomeric structures consistent with a pore and alters membrane permeability. Our analysis indicates that both the full-length HMPV SH protein and the isolated SH protein transmembrane domain can associate into higher-order oligomers. In addition, HMPV SH expression resulted in increases in permeability to hygromycin B and alteration of subcellular localization of a fluorescent dye, indicating that SH affects membrane permeability. These results suggest that the HMPV SH protein has several characteristics consistent with a putative viroporin. Interestingly, we also report that expression of the HMPV SH protein can significantly decrease HMPV F protein-promoted membrane fusion activity, with the SH extracellular domain and transmembrane domain playing a key role in this inhibition. These results suggest that the HMPV SH protein could regulate both membrane permeability and fusion protein function during viral infection. IMPORTANCE Human metapneumovirus (HMPV), first identified in 2001, is a causative agent of severe respiratory tract disease worldwide. The small hydrophobic (SH) protein is one of three glycoproteins encoded by all strains of HMPV, but the function of the HMPV SH protein is unknown. We have determined that the HMPV SH protein can alter the permeability of cellular membranes, suggesting that HMPV SH is a member of a class of proteins termed viroporins, which modulate membrane permeability to facilitate critical steps in a viral life cycle. We also demonstrated that HMPV SH can inhibit the membrane fusion function of the HMPV fusion protein. This work suggests that the HMPV SH protein has several functions, though the steps in the HMPV life cycle impacted by these functions remain to be clarified. |
| Databáze: | OpenAIRE |
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