T-CELLS EXPRESSING ACTIVATED LFA-1 ARE MORE SUSCEPTIBLE TO INFECTION WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PARTICLES BEARING HOST-ENCODED ICAM-1

The incorporation of host-derived proteins in nascent human immunodefi ciency virus type 1 (HIV-1) particles is a well-established phenomenon . We recently demonstrated that the physical presence of host-encoded ICAM-1 glycoproteins on HIV-1 leads to a significant increase in virus infectivity in an ICAM-1/LFA-1-dependent fashion (J.-F. Fortin, R. Ca ntin, G. Lamontagne, and M. Tremblay, J. Virol. 71:3588-3596, 1997). W e show here that conversion of LFA-1 to high affinity for ICAM-1 with the use of anti-LFA-l antibodies (clones NKI-L16 and MEM83) markedly e nhances the susceptibility of different target T-lymphoid cell lines, as well as of primary peripheral blood mononuclear cells, to infection by ICAM-1-bearing HIV-I particles (6- to 95-fold). It is known that T -cell receptor (TCR) cross-linking induces a transient increase in LFA -1 affinity for ICAM-1. Treatment of peripheral blood mononuclear cell s with anti-TCR antibodies (clone OKT3) resulted in a transient increa se in susceptibility to infection by ICAM-1-positive virions that para llels the previously reported kinetics of the LFA-1/ICAM-1 adhesion me chanism. Our results Led us to postulate that the strong interaction t aking place between virally incorporated ICAM-1 and cell surface-activ ated LFA-1 markedly enhances the efficiency of virus binding and entry , thus favoring greater infection by ICAM-1-bearing HIV-1 particles. I n view of the knowledge that primary HIV-1 isolates harbor host-derive d ICAM-1 on their surfaces, these results provide new information abou t the role of host-derived ICAM-1 in the life cycle of HIV-1 and how i t could positively modulate the dynamics of the viral infection, mainl y in cellular compartments, such as the lymphoid tissues, where the le vel of cellular activation is high and where the probability of encoun tering a T cell expressing the activated LFA-I form is also elevated.