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109 Study of the Mechanism(s) Playing a Role in the Selective Incorporation of Host ICAM-1 Protein into HIV-1
Y. Beauséjour* and M. J. Tremblay
Laval Univ., Ste-Foy, Québec, Canada
Background: Human immunodeficiency virus type 1 (HIV-1) acquires a vast array of host cell membrane proteins when the budding process take place in infected cells. The nature of the factor(s) responsible for the incorporation process of foreign constituents is still unknown. It has been postulated that a physical interaction between host membrane proteins and a virus-encoded molecule can dictate the process of incorporation.
Methods: In the present work, we used a transient transfection-and-expression system that allow us to produce virus particles differing only by the absence or the presence of virion-bound wild-type or mutated ICAM-1. Virus particles bearing mutations in the basic domain of the viral matrix protein that relocalize the Env proteins gp120 and gp41 and that consequently affect virus infectivity have been investigated for their ability to incorporate the membrane protein 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 cytoplasmic domain of ICAM-1 is also dispensable for the efficient incorporation of host ICAM-1 onto HIV-1. These data support the hypothesis that others interactions can direct the selective incorporation of ICAM-1.
Conclusions: These data show that HIV-1 actively acquires host-derived ICAM-1 in a process that is independent of viral Env and 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 important because it might have relevance for the development of new vaccine strategies.
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