Virion-bound ICAM-1 and activated LFA-1: a combination of factors conferring resistance to neutralization by sera from human immunodeficiency virus type 1-infected individuals independently of the disease status and phase.
The role of the supplementary interaction between virion-bound host ICAM-1 and LFA-1 on target cells in sensitivity to neutralization of human immunodeficiency virus type 1 (HIV-1) is poorly studied. Serum samples from four long-term nonprogressors (LTNPs) and sequential sera from one progressor were used to assess neutralization sensitivity of isogenic ICAM-1-negative and ICAM-1-bearing HIV-1(NL4-3), a prototype of T-cell-line-adapted viruses. We found that virus neutralization sensitivity to the studied sera is not modified by the additional interaction between virally embedded ICAM-1 and LFA-1 under an inactive state. However, expression on the target cell surface of an activated LFA-1 form renders ICAM-1-bearing virus particles, but not viruses devoid of ICAM-1, more refractory to neutralization by sera from three out of four LTNPs and all sequential sera from the person who has experienced a progression of the HIV-1-associated disease. Although no conclusive correlation could be drawn between virus susceptibility to neutralization and the disease status or stages of HIV-1 infection, these findings demonstrate that other nonspecific virus-cell interactions mediated by virion-anchored host proteins and their normal cognate ligands on target cells represent factors that can affect the mechanism of HIV-1 neutralization.
Losier
Martine
M
Centre de Recherche en Infectiologie, Hôpital CHUL, Centre Hospitalier Universitaire de Québec, and Département de Biologie médicale, Faculté de Médecine, Université Laval, G1V 4G2, Québec (QC), Canada.
Fortin
Jean François
JF
Cantin
Réjean
R
Bergeron
Michel G
MG
Tremblay
Michel J
MJ
D018791:CD4 Lymphocyte Count; D002460:Cell Line / Q000821:virology; D018450:Disease Progression; D004306:Dose-Response Relationship, Immunologic; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D008156:Luciferases; D016169:Lymphocyte Function-Associated Antigen-1 / Q000097:blood / Q000276:immunology*; D009500:Neutralization Tests / Q000379:methods*; D011485:Protein Binding; D015203:Reproducibility of Results; D019562:Viral Load / Q000379:methods
D015483:HIV Antibodies; D007106:Immune Sera; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D008156:Luciferases