Generation of lymphocyte cell lines coexpressing CD4 and wild-type or mutant HIV type 1 glycoproteins: implications for HIV type 1 Env-induced cell lysis.
To gain more insight into the processes leading to HIV-1 Env-induced cell death, we aim to coexpress stably wild-type and relevant mutant variants of both HIV-1 Env and human CD4 in lymphocyte cell lines. Here we report on the generation and characterization of several cell lines inducibly or constitutively expressing wild-type or cleavage-defective HIV-1 glycoproteins and human CD4 either singly or in combination. Coexpression of CD4 and wild-type Env led to the formation of multinucleated syncytia, to growth arrest and cell death, effects that all could be prevented by cultivation in the presence of monoclonal antibodies that inhibit cell surface membrane fusion. Cell lines coexpressing CD4 and mutated, noncleavable Env, detectable at the cell surface and still retaining CD4-binding capacity, were not retarded in their growth and cytolysis did not occur. These results indicate that cell lysis requires cell surface interaction of CD4 and gp120/41 and cleavage of gp160 to gp120 and gp41.
Krüger
U
U
Forschungsschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Pfeiffer
T
T
Bosch
V
V
D001402:B-Lymphocytes / Q000378:metabolism*; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016923:Cell Death; D002455:Cell Division; D003588:Cytopathogenic Effect, Viral; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D015752:Genes, env; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D019302:HIV Envelope Protein gp160 / Q000235:genetics* / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000473:pathology; D008561:Membrane Fusion; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013329:Structure-Activity Relationship; D014162:Transfection; D014407:Tumor Cells, Cultured
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D011993:Recombinant Fusion Proteins; D003907:Dexamethasone