Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Adhesion mediated by intercellular adhesion molecule 1 attenuates the potency of antibodies that block HIV-1 gp160-dependent syncytium formation.
AIDS Res Hum Retroviruses. 1994 May;10(5):585-93. Unique Identifier : AIDSLINE MED/95000931 Berman PW; Nakamura GR; Department of Immunology, Genentech, Inc., South San Francisco,; California 94080.
Abstract:
Several lines of evidence suggest that leukocyte adhesion molecules can promote HIV-1-mediated cell fusion and syncytium formation. In the present studies, the human kidney cell line, 293, was transfected with the envelope glycoprotein gene of the MN strain of HIV-1 alone or cotransfected with a cDNA encoding intercellular adhesion molecule 1 (ICAM-1). It was found that 293 cells transfected with the HIV-1MN env gene expressed the HIV-1 polyglycoprotein precursor, gp160, and the mature gp120-gp41 complex. When mixed with a CD4+ T cell line (CEM), the gp160-transfected cells mediated heterotypic cell fusion and formed multinucleate syncytia. Virus-neutralizing monoclonal antibodies to the V2 and V3 domains of gp120 were able to inhibit syncytium formation, as were monoclonal antibodies to CD4. When ICAM-1 was coexpressed with gp160, syncytium formation between the transfected kidney cells and uninfected CD$+ T cells was markedly enhanced. Inhibitors of HIV-1 infectivity (e.g., monoclonal antibodies to gp120, recombinant soluble CD4) were able to prevent syncytium formation; however, the syncytium-blocking activity of these agents was significantly attenuated in cultures in which ICAM-1 was cotransfected with gp160. These results confirm that leukocyte adhesion molecules can promote gp160-mediated syncytium formation and demonstrate, for the first time, that adhesive interactions mediated by ICAM-1 and its contrareceptor, LFA-1, attenuate the syncytium-inhibiting activity of virus-neutralizing monoclonal antibodies and soluble CD4. These findings suggest that the type and magnitude of leukocyte adhesion molecules expressed on cells may be a significant variable in in vitro HIV-1 neutralization assays.
Keywords: Binding, Competitive Cell Adhesion Cell Fusion Cell Line Cytopathogenic Effect, Viral Gene Products, env/GENETICS/*IMMUNOLOGY/PHYSIOLOGY Genes, env Human *HIV Antibodies HIV-1/GENETICS/*IMMUNOLOGY/PATHOGENICITY Intercellular Adhesion Molecule-1/*IMMUNOLOGY Lymphocyte Function-Associated Antigen-1/IMMUNOLOGY Protein Precursors/GENETICS/*IMMUNOLOGY/PHYSIOLOGY Transfection JOURNAL ARTICLE 950130
M9510840
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
