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Journal of Virology, June 1999, p. 5010-5017, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Polarized Human Immunodeficiency Virus Budding in Lymphocytes Involves a Tyrosine-Based Signal and Favors Cell-to-Cell Viral Transmission

Julie Deschambeault,1 Jean-Philippe Lalonde,1,2 Guillermo Cervantes-Acosta,1 Robert Lodge,1,dagger Éric A. Cohen,1 and Guy Lemay1,2,*

Département de Microbiologie et Immunologie1 and Groupe de Recherche en Transport Membranaire,2 Université de Montréal, Montréal, Québec H3C 3J7, Canada

Received 18 August 1998/Accepted 19 February 1999

Maturation and release of human immunodeficiency virus type 1 (HIV-1) is targeted at the pseudopod of infected mononuclear cells. However, the intracellular mechanism or targeting signals leading to this polarized viral maturation are yet to be identified. We have recently demonstrated the presence of a functional YXXL motif for specific targeting of HIV-1 virions to the basolateral membrane surface in polarized epithelial Madin-Darby canine kidney cells (MDCK). Site-directed mutagenesis was used to demonstrate that the membrane-proximal tyrosine in the intracytoplasmic tail of the HIV-1 transmembrane glycoprotein (gp41) is an essential component of this signal. In the present study, immunolocalization of viral budding allowed us to establish that this tyrosine-based signal is involved in determining the exact site of viral release at the surface of infected mononuclear cells. Substitution of the critical tyrosine residue was also shown to increase the amount of envelope glycoprotein at the cell surface, supporting previous suggestions that the tyrosine-based motif can promote endocytosis. Although alteration of the dual polarization-endocytosis motif did not affect the infectivity of cell-free virus, it could play a key role in cell-to-cell viral transmission. Accordingly, chronically infected lymphocytes showed a reduced ability to transmit the mutant virus to a cocultivated cell line. Overall, our data indicate that the YXXL targeting motif of HIV is active in various cell types and could play an important role in viral propagation; this may constitute an alternative target for HIV therapeutics and vaccine development.

* Corresponding author. Mailing address: Département de Microbiologie et Immunologie, Université de Montréal, P.O. Box 6128, Station centre-ville, Montréal, Québec, Canada H3C 3J7. Phone: (514) 343-2422. Fax: (514) 343-5701. E-mail: guy.lemay{at}umontreal.ca.

dagger Present address: Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-5430.

Journal of Virology, June 1999, p. 5010-5017, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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