Synergistic inhibition of HIV-1 envelope-mediated cell fusion by CD4-based molecules in combination with antibodies to gp120 or gp41.
AIDS Res Hum Retroviruses
; 9(7): 581-7, 1993 Jul.
Article
in En
| MEDLINE
| ID: mdl-8369162
ABSTRACT
CD4-based molecules were tested in combination with HIV-1-neutralizing antibodies directed against the V3 loop of gp120 or against gp41, for inhibition of HIV-1 envelope-mediated cell fusion. A virus-free cell fusion assay was developed, using Chinese hamster ovary cells that stably express HIV-1 gp120/gp41. These cells were incubated with dilutions of CD4-based molecules, antibodies, or mixtures of both, then overlaid with C8166 CD4+ T cells. Syncytia were counted and the degree of inhibition of cell fusion was determined. Synergy, additivity, or antagonism was calculated by the combination index (CI) method. The CD4-based molecules included soluble human CD4 as well as fusion proteins composed of CD4 linked to human immunoglobulin gamma 1 or gamma 2 heavy chains. Combinations of CD4-based molecules and monoclonal or polyclonal anti-V3 loop antibodies were synergistic in blocking HIV-1 envelope-mediated cell fusion (CI = 0.21-0.91 at 95% inhibition). Synergy was also observed with combinations of the CD4-based molecules and a broadly neutralizing anti-gp41 monoclonal antibody (2F5) (CI = 0.29-0.65 at 95% inhibition). These results demonstrate that molecules inhibiting HIV attachment act synergistically with molecules inhibiting HIV-1 fusion. The results suggest that CD4-based therapeutics would be more effective in patients with naturally occurring anti-V3 loop or anti-gp41 antibodies. In addition, there may be an advantage in coadministering CD4-based molecules and antibodies that block fusion, especially broadly neutralizing anti-gp41 antibodies, as a combination therapy for HIV-1 infections.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
HIV Antibodies
/
CD4 Antigens
/
Gene Products, env
/
Giant Cells
/
HIV-1
/
CD4 Immunoadhesins
Limits:
Animals
/
Humans
Language:
En
Journal:
AIDS Res Hum Retroviruses
Journal subject:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Year:
1993
Document type:
Article