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Journal of Virology, July 2005, p. 9244-9253, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.9244-9253.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Protease-Dependent Uncoating of a Complex Retrovirus{dagger}

Jacqueline Lehmann-Che,1 Marie-Lou Giron,1 Olivier Delelis,2 Martin Löchelt,3 Patricia Bittoun,1 Joelle Tobaly-Tapiero,1 Hugues de Thé,1 and Ali Saïb1*

CNRS UMR 7151—Université Paris 7, Hôpital Saint Louis, 75010 Paris,1 INSERM U567, Paris, France,2 Abt Genomveranderung und Carcinogenese, DKFZ, Heidelberg, Germany3

Received 15 November 2004/ Accepted 11 March 2005

Although retrovirus egress and budding have been partly unraveled, little is known about early stages of the replication cycle. In particular, retroviral uncoating, a process during which incoming retroviral cores are altered to allow the integration of the viral genome into host chromosomes, is poorly understood. To get insights into these early events of the retroviral cycle, we have used foamy complex retroviruses as a model. In this report, we show that a protease-defective foamy retrovirus is noninfectious, although it is still able to bud and enter target cells efficiently. Similarly, a retrovirus mutated in an essential viral protease-dependent cleavage site in the central part of Gag is noninfectious. Following entry, wild-type and mutant retroviruses are able to traffic along microtubules towards the microtubule-organizing center (MTOC). However, whereas nuclear import of Gag and of the viral genome was observed for the wild-type virus as early as 8 hours postinfection, incoming capsids and genome from mutant viruses remained at the MTOC. Interestingly, a specific viral protease-dependent Gag cleavage product was detected only for the wild-type retrovirus early after infection, demonstrating that cleavage of Gag by the viral protease at this stage of the virus life cycle is absolutely required for productive infection, an unprecedented observation among retroviruses.

* Corresponding author. Mailing address: CNRS UMR7151, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France. Phone: 33.1.53.72.40.96. Fax: 33.1.53.72.40.90. E-mail: alisaib{at}infobiogen.fr.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, July 2005, p. 9244-9253, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.9244-9253.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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