A soluble factor secreted by an HIV-1-resistant cell line blocks transcription through inactivating the DNA-binding capacity of the NF-κB p65/p50 dimer

Adam Lesner, Yuchang Li, Jadwiga Nitkiewicz, Guanhua Li, Alex Kartvelishvili, Magdalena Kartvelishvili, Malgorzata Simm

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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 HTV-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-κB. In the present report we identified the site at which HRF exerts this inhibition by evaluating a set of discrete events in NF-κB action. We tested the κB 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 κB oligonucleotide in vitro as affected by prior or simultaneous exposure to HRF. The results of this experimental schema indicate that HRF interacts with pSO after it enters the nucleus, but before its binding to DNA and that this interaction impedes the formation of an NF-κB-DNA complex required for the promotion of transcription. These findings suggest that HRF mediates a novel innate immune response to virus infection.

Original languageEnglish
Pages (from-to)2548-2554
Number of pages7
JournalJournal of Immunology
Volume175
Issue number4
DOIs
StatePublished - 15 Aug 2005
Externally publishedYes

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