A soluble factor secreted by an HIV-1-resistant cell line blocks transcription through inactivating the DNA-binding capacity of the NF-kappa B p65/p50 dimer.
The identity and activity of several anti-HIV soluble factor(s) secreted by CD8 and CD4 T lymphocytes have been determined; however, some of them still await definition. We have established an HIV-1-resistant, transformed CD4 T cell line that secretes HIV-1 resistance protein(s). Our studies indicate that this protein(s), called HIV-1 resistance factor (HRF), inhibits transcription of the virus by interfering with the activity of NF-kappaB. In the present report we identified the site at which HRF exerts this inhibition by evaluating a set of discrete events in NF-kappaB action. We tested the kappaB oligonucleotide binding activity in nuclei of resistant cells, nuclear translocation and binding to the HIV-1 long terminal repeat of p65 and p50 proteins from susceptible cells after exposure to HRF, and the binding of recombinant p50 to the kappaB oligonucleotide in vitro as affected by prior or simultaneous exposure to HRF. The results of this experimental schema indicate that HRF interacts with p50 after it enters the nucleus, but before its binding to DNA and that this interaction impedes the formation of an NF-kappaB-DNA complex required for the promotion of transcription. These findings suggest that HRF mediates a novel innate immune response to virus infection.
Lesner
Adam
A
Molecular Virology Division, St. Luke's-Roosevelt Hospital Center, Columbia University Medical Center, New York, NY 10019, USA.
Li
Yuchang
Y
Nitkiewicz
Jadwiga
J
Li
Guanhua
G
Kartvelishvili
Alex
A
Kartvelishvili
Magdalena
M
Simm
Malgorzata
M
D021581:Active Transport, Cell Nucleus / Q000276:immunology; D019380:Anti-HIV Agents / Q000378:metabolism* / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002461:Cell Line, Transformed; D004247:DNA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019281:Dimerization; D024882:Drug Resistance, Viral; D020868:Gene Silencing; D016325:HIV Long Terminal Repeat / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology; D012995:Solubility; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology*
D019380:Anti-HIV Agents; D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; D004247:DNA