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Journal of Virology, February 2005, p. 1992-2000, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.1992-2000.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Adenovirus Protein VI Mediates Membrane Disruption following Capsid Disassembly

Christopher M. Wiethoff,1 Harald Wodrich,2 Larry Gerace,3 and Glen R. Nemerow1*

Departments of Immunology,1 Cell Biology, The Scripps Research Institute, La Jolla, California,3 Institut de Génétique de Montpellier, Montpellier, France2

Received 13 July 2004/ Accepted 29 September 2004

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 {alpha}-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.

* Corresponding author. Mailing address: Department of Immunology, IMM-19, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-8072. Fax: (858) 784-8472. E-mail: gnemerow{at}scripps.edu.

Journal of Virology, February 2005, p. 1992-2000, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.1992-2000.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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