Interaction between virion-bound host intercellular adhesion molecule-1 and the high-affinity state of lymphocyte function-associated antigen-1 on target cells renders R5 and X4 isolates of human immunodeficiency virus type 1 more refractory to neutralization

The oligomeric nature of the viral envelope proteins has been partly held r esponsible for the observed differences in neutralization sensitivity betwe en primary and laboratory-adapted strains of human immunodeficiency Virus t ype 1 (HIV-1). However, recent evidence suggests that host factors can also modify the sensitivity of HIV-1 particles to neutralization. Having previo usly demonstrated that the acquisition of host-encoded intercellular adhesi on molecule (ICAM)-1 proteins by newly formed Viruses has a functional sign ificance for the life cycle of HIV-1, we investigated whether the acquisiti on of host-derived ICAM-1 by HIV-1 could affect the virus sensitivity to ne utralization. In this study, we have first shown that the physical presence of host cell membrane ICAM-1 on HIV-1 was not modifying virus sensitivity to neutralization by either two different anti-gp120 monoclonal antibodies (0.5 beta and 4.8D) or soluble CD4. However, the ability of the F105 anti-g p120 monoclonal antibody (specific for the CD4-binding site) to neutralize ICAM-1-bearing virions was diminished when target were pretreated with an l ymphocyte function-associated antigen-1 (LFA-1)-activating antibody. Intere stingly, ICAM-1/ POS progeny viruses were found to be slightly more resista nt to neutralization by individual human sera in target cells expressing a low-affinity form of LFA-1 than viruses devoid of host-encoded ICAM-1 prote ins. This resistance was markedly enhanced when target cells expressed an a ctivated LFA-1 form on their surface. These results suggest that the intera ction between virally embedded host ICAM-1 and target cell surface LFA-1 sh ould be considered a factor modulating neutralization sensitivity of HIV-1 by human sera from HIV-1-infected individuals. (C) 2000 Academic Press.