title: 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.
abstract: The oligomeric nature of the viral envelope proteins has been partly held responsible for the observed differences in neutralization sensitivity between primary and laboratory-adapted strains of human immunodeficiency virus type 1 (HIV-1). However, recent evidence suggests that host factors can also modify the sensitivity of HIV-1 particles to neutralization. Having previously demonstrated that the acquisition of host-encoded intercellular adhesion molecule (ICAM)-1 proteins by newly formed viruses has a functional significance for the life cycle of HIV-1, we investigated whether the acquisition of host-derived ICAM-1 by HIV-1 could affect the virus sensitivity to neutralization. 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 (0.5beta and 4.8D) or soluble CD4. However, the ability of the F105 anti-gp120 monoclonal antibody (specific for the CD4-binding site) to neutralize ICAM-1-bearing virions was diminished when target cells were pretreated with an lymphocyte function-associated antigen-1 (LFA-1)-activating antibody. Interestingly, ICAM-1/POS progeny viruses were found to be slightly more resistant 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 proteins. This resistance was markedly enhanced when target cells expressed an activated LFA-1 form on their surface. These results suggest that the interaction between virally embedded host ICAM-1 and target cell surface LFA-1 should be considered a factor modulating neutralization sensitivity of HIV-1 by human sera from HIV-1-infected individuals.
authors.affiliation: Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, and, Ste-Foy, Québec, G1V 4G2, Canada.
authors.forename: J F
authors.initials: JF
authors.lastname: Fortin
authors.forename: R
authors.initials: R
authors.lastname: Cantin
authors.forename: M G
authors.initials: MG
authors.lastname: Bergeron
authors.forename: M J
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002460:Cell Line; D017930:Genes, Reporter / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification* / Q000378:metabolism; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008875:Middle Aged; D009500:Neutralization Tests; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D014771:Virion / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D007106:Immune Sera; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D008156:Luciferases