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Journal of Virology, June 1999, p. 5079-5088, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Oligomerization within Virions and Subcellular Localization of Human Immunodeficiency Virus Type 1 Integrase

Caroline Petit,1,2 Olivier Schwartz,2 and Fabrizio Mammano3,*

Unité d'Oncologie Virale1 and Unité Rétrovirus et Transfert Génétique,2 Institut Pasteur, and Laboratoire de Recherche Antivirale, INSERM U82,3 Paris, France

Received 25 November 1998/Accepted 12 March 1999

Previous biochemical and genetic evidence indicated that the functional form of retroviral integrase protein (IN) is a multimer. A direct demonstration of IN oligomerization during the infectious cycle was, however, missing, due to the absence of a sensitive detection method. We describe here the generation of infectious human immunodeficiency virus type 1 (HIV-1) viral clones carrying IN protein tagged with highly antigenic epitopes. In this setting, we could readily visualize IN both in producer cells and in viral particles. More interestingly, we detected IN oligomers, the formation of which was dependent on disulfide bridges and took place inside virions. Additionally, expression of a tagged HIV-1 IN in the absence of other viral components resulted in almost exclusive nuclear accumulation of the protein. Mutation of a conserved cysteine in the proposed dimer interface determined the loss of viral infectivity, associated with a reduction of IN oligomer formation and the redistribution of the mutated protein in the nucleus and cytoplasm. Epitope tagging of HIV-1 IN expressed alone or in the context of a replication-competent viral clone provides powerful tools to validate debated issues on the implication of this enzyme in different steps of the viral cycle.

* Corresponding author. Mailing address: Laboratoire de Recherche Antivirale, IMEA/INSERM Hôpital Bichat-Claude Bernard, 46 rue H. Huchard, 75018 Paris, France. Phone: 33-1-4025 6359. Fax: 33-1-4025 6351. E-mail: mammano{at}bichat.inserm.fr.

Journal of Virology, June 1999, p. 5079-5088, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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