PubMed · 2297202
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E C Tramont, R R Redfield. 1990-02-15. Soluble CD4: the first step.. https://doi.org/10.7326/0003-4819-112-4-241
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A series of cationic metalloporphyrin-ellipticine complexes were found to inhibit the cytopathicity of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus in MT-4 cells at concentrations ranging from 1.4 to 17 micrograms/mL, i.e. at a concentration that was 2.5-30-fold below the cytotoxicity threshold. These compounds were also found to inhibit syncytium formation between persistently HIV-1-infected HUT-78 and uninfected Molt/4 cells, to interfere with HIV-1 binding to the cells, and to suppress HIV-1-associated reverse transcriptase activity.
Gangliosides induce a selective and complete modulation of CD4 from the surface of T cells. CD4 down-modulation occurs by CD4 endocytosis. This process is independent of serine phosphorylation of the cytoplasmic tail of CD4 and does not require the association between the tyrosine protein kinase p56lck and the cytoplasmic tail of CD4. Ganglioside-induced CD4 endocytosis is accompanied by the loss of p56lck activity associated with CD4. Sequential immunoprecipitation analysis using an anti-CD4 antibody and an anti-p56lck antiserum showed that this is caused by the dissociation of the enzyme from the cytoplasmic tail of CD4. The kinetics of p56lck dissociation after ganglioside treatment is identical to that of CD4 endocytosis, suggesting that p56lck is displaced in the process of endosome formation. The results indicate that CD4 endocytosis alone can cause the dissociation of the p56lck complex without the requirement for CD4 phosphorylation.