176-M. Role of the Viral Envelope-Matrix Complex and Host Cytoskeleton in the Selective Incorporation of Host ICAM-1 Protein into HIV-1

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Session 38 Poster Session
Viral and Cellular Proteins on the Virion Surface
Session Time: 4:30-6:30 pm
Room 4E-F

176-M.

Role of the Viral Envelope-Matrix Complex and Host Cytoskeleton in the Selective Incorporation of Host ICAM-1 Protein into HIV-1
Y. Beauséjour* and M. J. Tremblay
Univ. Laval, Ste-Foy, QC, Canada

Background: Human immunodeficiency virus type 1 (HIV-1) acquires a vast array of host cell proteins when the budding process takes place in infected cells. However, the nature of factor(s) responsible for the incorporation of foreign constituents remains a matter of speculation. It has been postulated that a physical interaction between host membrane proteins and virus-encoded molecules can dictates the process of incorporation.
Methods: In the present work, we used a transient transfection-and-expression system that allows us to produce virus particles differing only by the absence or the presence of virion-bound ICAM-1. Virus particles bearing mutation in Pr55gag MA that significantly reduce the level of viral Env proteins in virions and that consequently affects viral infectivity has been investigated for their ability to incorporate ICAM-1. We also used a sensitive single-cycle infection assay based on a cell line expressing an LTR-luciferase cDNA construct to compare the infectivity of virions that bear different incorporated proteins.
Results: In contrast to HLA-DR that requires the presence of Env protein for its efficient incorporation into the membrane of nascent HIV-1, ICAM-1 does not need any interaction with the gp120 and gp41 proteins. Moreover, the presence of ICAM-1 into HIV-1 with suboptimal level of gp120 allows viral replication in an ICAM-1/LFA-1-dependent fashion. Furthermore, the intracytoplasmic domain of ICAM-1 contribute to its efficient incorporation into HIV-1. These data support the hypothesis that a direct interaction between the cytoskeleton and the cytoplasmic tail of ICAM-1 could lead to the selective incorporation of this adhesion molecule into HIV-1.
Conclusions: These data demonstrate that the presence of ICAM-1 into HIV-1 particules, containing suboptimal amount of gp120 permits a faster viral replication for cells that express the counterreceptor LFA-1. Moreover, these data show that HIV-1 actively acquires host-derived ICAM-1 in a process that is independent of viral Env, but dependent of the cytoplasmic tail of ICAM-1. A better understanding of the factor(s) involved in the incorporation process of host proteins in the HIV-1 envelope is essential because it might have relevance for the development of new vaccine strategies.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections