Correlation between kinetics of soluble CD4 interactions with HIV-1-Env-expressing cells and inhibition of syncytia formation: implications for mechanisms of cell fusion and therapy for AIDS.

Abstract

OBJECTIVES:

To study the kinetics of the interactions between soluble (s) CD4 and HIV-1-Env-expressing cells in relation to subsequent events leading to cell fusion and inhibition of syncytia formation.

DESIGN:

Vaccinia-HIV-1 (Env)-infected CD4- T-cells were used to study the kinetics of sCD4-gp120/41 interactions and syncytia formation (with CD4+ T-cells) under identical conditions.

METHODS:

sCD4 association and dissociation rates for HIV-1-Env-expressing cells, and quantification of sCD4-induced gp120 shedding was determined by a quantitative flow cytometry assay. Syncytia inhibition was measured in the continuous presence of sCD4, or after washing of HIV-1-Env-expressing cells following pre-incubation with sCD4.

RESULTS:

The kinetics of syncytia inhibition correlated with sCD4 binding when sCD4 was maintained during the culture. When Env-expressing cells, which had been pre-incubated with sCD4, were washed to remove unbound sCD4, no syncytia formation inhibition was observed, even following sCD4-induced shedding of greater than 50% of surface gp120 molecules.

CONCLUSIONS:

The lack of syncytia inhibition seen after removal of unbound sCD4, even after pre-incubation of cells under saturation and gp120 shedding conditions, indicated that sufficient numbers of fusogenic molecules remained on the sCD4-treated cells. In addition, fast dissociation of pre-bound sCD4 occurred in culture. These results are important for understanding HIV-1-Env-mediated cell fusion and AIDS therapy.

• Authors: D S Dimitrov, K Hillman, J Manischewitz, R Blumenthal, H Golding
• Journal: AIDS (London, England) (AIDS) Vol. 6 Issue 3 Pg. 249-56 (Mar 1992) ISSN: 0269-9370 [Print] England
• PMID: 1348943 (Publication Type: Journal Article)

Chemical References

• Antigens, Surface
• CD4 Antigens
• HIV Envelope Protein gp120
• HIV Envelope Protein gp41

Topics

• Acquired Immunodeficiency Syndrome (therapy)
• Antigens, Surface (metabolism)
• CD4 Antigens (metabolism)
• CD4-Positive T-Lymphocytes (cytology, metabolism)
• Cell Line
• Flow Cytometry
• Giant Cells (cytology, metabolism)
• HIV Envelope Protein gp120 (metabolism)
• HIV Envelope Protein gp41 (metabolism)
• HIV-1 (metabolism)
• Humans
• Kinetics
• Membrane Fusion (physiology)