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7005581 
Journal Article 
Adenovirus protein VI mediates membrane disruption following capsid disassembly 
Wiethoff, CM; Wodrich, H; Gerace, L; Nemerow, GR; , 
2005 
1 
Journal of Virology
ISSN: 0022-538X
EISSN: 1098-5514 
AMER SOC MICROBIOLOGY 
WASHINGTON 
1992-2000 
English 
15681401 
WOS:000226772100002 
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.