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Virus-Cell Interactions

Adenovirus Protein VI Mediates Membrane Disruption following Capsid Disassembly

Christopher M. Wiethoff, Harald Wodrich, Larry Gerace, Glen R. Nemerow
Christopher M. Wiethoff
1Departments of Immunology
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Harald Wodrich
2Institut de Génétique de Montpellier, Montpellier, France
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Larry Gerace
3Cell Biology, The Scripps Research Institute, La Jolla, California
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Glen R. Nemerow
1Departments of Immunology
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  • For correspondence: gnemerow@scripps.edu
DOI: 10.1128/JVI.79.4.1992-2000.2005
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ABSTRACT

In contrast to enveloped viruses, the mechanisms involved in membrane penetration by nonenveloped viruses are not as well understood. In these studies, we determined the relationship between adenovirus (Ad) capsid disassembly and the development of membrane lytic activity. Exposure to low pH or heating induced conformational changes in wild-type Ad but not in temperature-sensitive Ad (ts1) particles that fail to escape the early endosome. Wild-type Ad but not ts1 particles permeabilized model membranes (liposomes) and facilitated the cytosolic delivery of a ribotoxin. Alterations in wild-type Ad capsids were associated with the exposure of a pH-independent membrane lytic factor. Unexpectedly, this factor was identified as protein VI, a 22-kDa cement protein located beneath the peripentonal hexons in the viral capsid. Recombinant protein VI and preprotein VI, but not a deletion mutant lacking an N-terminal amphipathic α-helix, possessed membrane lytic activity similar to partially disassembled virions. A new model of Ad entry is proposed based on our present observations of capsid disassembly and membrane penetration.

  • Copyright © 2005 American Society for Microbiology
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Adenovirus Protein VI Mediates Membrane Disruption following Capsid Disassembly
Christopher M. Wiethoff, Harald Wodrich, Larry Gerace, Glen R. Nemerow
Journal of Virology Jan 2005, 79 (4) 1992-2000; DOI: 10.1128/JVI.79.4.1992-2000.2005

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Adenovirus Protein VI Mediates Membrane Disruption following Capsid Disassembly
Christopher M. Wiethoff, Harald Wodrich, Larry Gerace, Glen R. Nemerow
Journal of Virology Jan 2005, 79 (4) 1992-2000; DOI: 10.1128/JVI.79.4.1992-2000.2005
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KEYWORDS

Adenoviridae
Capsid Proteins
Cell Membrane
virion

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