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Journal of Virology, December 2004, p. 13573-13581, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.13573-13581.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Furin-Mediated Cleavage of the Feline Foamy Virus Env Leader Protein

Verena Geiselhart,1 Patrizia Bastone,1 Tore Kempf,2 Martina Schnölzer,2 and Martin Löchelt1*

Abt. Genomveränderung und Carcinogenese, Forschungsschwerpunkt Infektion und Krebs,1 Zentrale Proteinanalytik, Deutsches Krebsforschungszentrum, Heidelberg, Germany2

Received 11 May 2004/ Accepted 19 July 2004

The molecular biology of spuma or foamy retroviruses is different from that of the other members of the Retroviridae. Among the distinguishing features, the N-terminal domain of the foamy virus Env glycoprotein, the 16-kDa Env leader protein Elp, is a component of released, infectious virions and is required for particle budding. The transmembrane protein Elp specifically interacts with N-terminal Gag sequences during morphogenesis. In this study, we investigate the mechanism of Elp release from the Env precursor protein. By a combination of genetic, biochemical, and biophysical methods, we show that the feline foamy virus (FFV) Elp is released by a cellular furin-like protease, most likely furin itself, generating an Elp protein consisting of 127 amino acid residues. The cleavage site fully conforms to the rules for an optimal furin site. Proteolytic processing at the furin cleavage site is required for full infectivity of FFV. However, utilization of other furin proteases and/or cleavage at a suboptimal signal peptidase cleavage site can partially rescue virus viability. In addition, we show that FFV Elp carries an N-linked oligosaccharide that is not conserved among the known foamy viruses.


* Corresponding author. Mailing address: Abt. Genomveränderung und Carcinogenese, Forschungsschwerpunkt Infektion und Krebs, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany. Phone: 49 6221 42 4933. Fax: 49 6221 42 4932. E-mail: m.loechelt{at}dkfz-heidelberg.de.


Journal of Virology, December 2004, p. 13573-13581, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.13573-13581.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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