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J Virol, May 1998, p. 3845-3850, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Antiviral Activity of the Proteasome on Incoming Human Immunodeficiency Virus Type 1

Olivier Schwartz,1,* Valérie Maréchal,1 Bertrand Friguet,2 Fernando Arenzana-Seisdedos,3 and Jean-Michel Heard1

Laboratoire Rétrovirus et Transfert Génétique, URA CNRS 1157,1 Unité de Biochimie Cellulaire,2 and Unité d'Immunologie Virale,3 Institut Pasteur, 75724 Paris Cedex 15, France

Received 18 November 1997/Accepted 3 February 1998

Following cell surface receptor binding and membrane fusion, human immunodeficiency virus (HIV) virion cores are released in the cytoplasm. Incoming viral proteins represent potential targets for cytosolic proteases. We show that treatment of target cells with the proteasome inhibitors MG132 and lactacystin increased the efficiency of HIV infection. Proteasome inhibitors were active at the early steps of the viral cycle. Incoming p24Gag proteins accumulated in the cytosol, and larger amounts of proviral DNA were synthesized. In vitro, purified 20S proteasome degraded HIV virion components. Thus, degradation of incoming viral proteins by the proteasome represents an early intracellular defense against infection.

* Corresponding author. Mailing address: Laboratoire Retrovirus et Transfert Génétique, URA CNRS 1157, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: 33 (1) 45 68 83 53. Fax: 33 (1) 45 68 89 40. E-mail: schwartz{at}pasteur.fr.

J Virol, May 1998, p. 3845-3850, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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