HOST-DERIVED ICAM-1 GLYCOPROTEINS INCORPORATED ON HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ARE BIOLOGICALLY-ACTIVE AND ENHANCE VIRAL INFECTIVITY

Human immunodeficiency virus type 1 (HIV-1) acquires several host cell membrane proteins when it buds from infected cells, To study the effe ct of virally incorporated host-derived ICAM-1 glycoproteins on the bi ology of HIV-1, we have developed a transient expression system that h as enabled us to produce virus particles differing only in the absence or the presence of virion-bound ICAM-1. By using a single-round infec tion assay based on an ICAM-1-negative target T-cell line stably trans fected with an HIV-1 long terminal repeat driven luciferase gene const ruct, we have been able to demonstrate that the acquisition of host-de rived ICAM-1 by HIV-1 has functional significance, since it leads to a pronounced increase in viral infectivity (4.6- to 9.8-fold) in an ICA M-1/LFA-1-dependent fashion, as shown by blocking with anti-ICAM-1 and -LFA-1 antibodies. The same potentiating effect on viral infectivity was also observed with monocytoid cells, Studies of the kinetics of in fection revealed that the positive effect mediated by virally embedded host cell membrane ICAM-1 is due to an increase in the efficiency of early steps in the viral life cycle, These results provide new insight s into how incorporation of host proteins can modulate the biological properties of HIV-1, Our findings have direct clinical relevance, cons idering that ICAM-1 is expressed on the surface of virus-infected cell s and, more importantly, that host-derived ICAM-1 has been shown to be acquired by clinical HIV-1 isolates grown on primary mononuclear cell s. These data justify a more complete analysis of the other putative r ole(s) that virally incorporated ICAM-1 may play in the life cycle of HIV-1, for example, at the level of neutralization sensitivity.