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Biophys J. 2014 Apr 1;106(7):1447-56. doi: 10.1016/j.bpj.2014.02.018.
pH-Controlled Two-Step Uncoating of Influenza Virus.
Li S1, Sieben C2, Ludwig K3, H?fer CT2, Chiantia S2, Herrmann A4, Eghiaian F5, Schaap IA6.
Author information
Abstract
Upon endocytosis in its cellular host, influenza A virus transits via early to late endosomes. To efficiently release its genome, the composite viral shell must undergo significant structural rearrangement, but the exact sequence of events leading to viral uncoating remains largely speculative. In addition, no change in viral structure has ever been identified at the level of early endosomes, raising a question about their role. We performed AFM indentation on single viruses in conjunction with cellular assays under conditions that mimicked gradual acidification from early to late endosomes. We found that the release of the influenza genome requires sequential exposure to the pH of both early and late endosomes, with each step corresponding to changes in the virus mechanical response. Step 1 (pH 7.5-6) involves a modification of both hemagglutinin and the viral lumen and is reversible, whereas Step 2 (pH <6.0) involves M1 dissociation and major hemagglutinin conformational changes and is irreversible. Bypassing the early-endosomal pH step or blocking the envelope proton channel M2 precludes proper genome release and efficient infection, illustrating the importance of viral lumen acidification during the early endosomal residence for influenza virus infection.
Copyright ? 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.
PMID:
24703306
[PubMed - in process]
pH-Controlled Two-Step Uncoating of Influenza Virus.
Li S1, Sieben C2, Ludwig K3, H?fer CT2, Chiantia S2, Herrmann A4, Eghiaian F5, Schaap IA6.
Author information
Abstract
Upon endocytosis in its cellular host, influenza A virus transits via early to late endosomes. To efficiently release its genome, the composite viral shell must undergo significant structural rearrangement, but the exact sequence of events leading to viral uncoating remains largely speculative. In addition, no change in viral structure has ever been identified at the level of early endosomes, raising a question about their role. We performed AFM indentation on single viruses in conjunction with cellular assays under conditions that mimicked gradual acidification from early to late endosomes. We found that the release of the influenza genome requires sequential exposure to the pH of both early and late endosomes, with each step corresponding to changes in the virus mechanical response. Step 1 (pH 7.5-6) involves a modification of both hemagglutinin and the viral lumen and is reversible, whereas Step 2 (pH <6.0) involves M1 dissociation and major hemagglutinin conformational changes and is irreversible. Bypassing the early-endosomal pH step or blocking the envelope proton channel M2 precludes proper genome release and efficient infection, illustrating the importance of viral lumen acidification during the early endosomal residence for influenza virus infection.
Copyright ? 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.
PMID:
24703306
[PubMed - in process]
