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pH regulation in early endosomes and interferon-inducible transmembrane proteins control avian retrovirus fusion
- Source :
- Journal of Biological Chemistry. 292:7817-7827
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Enveloped viruses infect host cells by fusing their membranes with those of the host cell, a process mediated by viral glycoproteins upon binding to cognate host receptors or entering into acidic intracellular compartments. Whereas the effect of receptor density on viral infection has been well studied, the role of cell type-specific factors/processes, such as pH regulation, has not been characterized in sufficient detail. Here, we examined the effects of cell-extrinsic factors (buffer environment) and cell-intrinsic factors (interferon-inducible transmembrane proteins, IFITMs), on the pH regulation in early endosomes and on the efficiency of acid-dependent fusion of the avian sarcoma and leukosis virus (ASLV), with endosomes. First, we found that a modest elevation of external pH can raise the pH in early endosomes in a cell type-dependent manner and thereby delay the acid-induced fusion of endocytosed ASLV. Second, we observed a cell type-dependent delay between the low pH-dependent and temperature-dependent steps of viral fusion, consistent with the delayed enlargement of the fusion pore. Third, ectopic expression of IFITMs, known to potently block influenza virus fusion with late compartments, was found to only partially inhibit ASLV fusion with early endosomes. Interestingly, IFITM expression promoted virus uptake and the acidification of endosomal compartments, resulting in an accelerated fusion rate when driven by the glycosylphosphatidylinositol-anchored, but not by the transmembrane isoform of the ASLV receptor. Collectively, these results highlight the role of cell-extrinsic and cell-intrinsic factors in regulating the efficiency and kinetics of virus entry and fusion with target cells.
- Subjects :
- Gene Expression Regulation, Viral
0301 basic medicine
Endosome
Viral protein
Endosomes
medicine.disease_cause
Membrane Fusion
Microbiology
Biochemistry
Avian sarcoma virus
Cell Line
03 medical and health sciences
Retrovirus
Viral envelope
Viral entry
medicine
Animals
Humans
Protein Isoforms
Transport Vesicles
Molecular Biology
030102 biochemistry & molecular biology
biology
Temperature
Membrane Proteins
RNA-Binding Proteins
Lipid bilayer fusion
Cell Biology
Hydrogen-Ion Concentration
Virus Internalization
biology.organism_classification
Fusion protein
Endocytosis
Cell biology
HEK293 Cells
030104 developmental biology
Avian Sarcoma Viruses
A549 Cells
Receptors, Virus
Acids
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 292
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....1619d3d2f616795a77059bda55f1d8ac