HIV-1 gp120/160 expressing cells upregulate HIV-1 LTR directed gene expression in a cell line transfected with HIV-1 LTR-reporter gene constructs.
The results described in this paper demonstrate that HIV-1 gp120 can upregulate gene expression directed by the HIV-1 LTR. Briefly, exposing responder CD4+CEM-T4 ID5 cells to stimulator CEMgp120/160 expressing cells (stably transfected with HIV-1 LTR-CAT and HIV-1 gp160, respectively) resulted in the increased synthesis of the CAT enzyme. Control non-transfected CEM-T4 cells did not induce the synthesis of CAT. In addition, when the responder cell line, U937-1C5 which also contains stably transfected HIV-1 LTR-CAT plasmid was exposed to irradiated CEM gp120/160 cells, there was no synthesis of the CAT enzyme. Neither recombinant gp120 nor gp160 were able to stimulate the synthesis of CAT in the responder cells. These results indicate that the mechanism by which gp120/160 expressed on transfected cells increase CAT synthesis in responder cells may be dependent on the manner which the protein is presented in association with accessory molecules. Moreover, recombinant soluble CD4 and anti-CD4 monoclonal antibodies inhibited CEM gp120/160 induced expression of HIV-1 LTR-directed expression in CEM-1D5 cells. Based on these results we hypothesize that HIV or its envelope protein, gp120, upon interaction with its receptor, the CD4 molecule on T helper cells, transduces a signal which translates into the upregulation of the gene expression directed by the HIV-1 LTR.
Merzouki
A
A
Virology Research Center Institut Armand-Frappier, Laval, Quebec, Canada.
Patel
P
P
Cassol
S
S
Ennaji
M
M
Tailor
P
P
Turcotte
F R
FR
O'Shaughnessy
M
M
Arella
M
M
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line / Q000528:radiation effects; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral; D015686:Gene Products, env / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D013755:Tetradecanoylphorbol Acetate