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Absolute dependence on kappa B responsive elements for initiation and Tat-mediated amplification of HIV transcription in blood CD4 T lymphocytes.
EMBO J 1995; 14(7):1552-60EJ

Abstract

The role of NF-kappa B-dependent signals in activating the transcriptional activity of the HIV regulatory region (LTR) was analyzed by systematic comparison of HIV LTR activity in human CD4 T cells purified from peripheral blood and a transformed lymphoblastoid T cell line. In normal CD4 T cells we also analyzed the role played by the viral kappa B responsive elements in HIV replication. Analysis of nuclear extracts of resting, normal T lymphocytes revealed the presence of the p50, but not the p65, NF-kappa B subunit and the induction by phorbol esters of bona fide (p50-p65) NF-kappa B complexes. In parallel, we observed clear enhancer-dependent HIV LTR transactivation comparable in intensity with that observed in lymphoblastoid cells. We show that unstimulated CD4 T lymphocytes offer a cellular environment of very low permissivity to HIV LTR functioning. This was in sharp contrast to the high spontaneous LTR activity observed in lymphoblastoid T cells, where LTR activity was essentially independent of kappa B-responsive elements. Due to the low basal LTR activity in resting T lymphocytes, NF-kappa B-dependent transactivation was a sine qua non event for induction of the HIV LTR. Surprisingly, even the function of HIV Tat in resting CD4 T lymphocytes was found to be absolutely dependent on LTR kappa B responsive elements. The relevance of these observations obtained in transient transfections was confirmed by the incapacity of blood CD4 T lymphocytes infected with an HIV infectious provirus carrying critical point mutations in the kappa B responsive elements to show any detectable transcriptional activity upon cell activation and prolonged culture in vitro.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Servicio de Microbiología, Hospital 12 de Octubre, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7729429

Citation

Alcamí, J, et al. "Absolute Dependence On Kappa B Responsive Elements for Initiation and Tat-mediated Amplification of HIV Transcription in Blood CD4 T Lymphocytes." The EMBO Journal, vol. 14, no. 7, 1995, pp. 1552-60.
Alcamí J, Laín de Lera T, Folgueira L, et al. Absolute dependence on kappa B responsive elements for initiation and Tat-mediated amplification of HIV transcription in blood CD4 T lymphocytes. EMBO J. 1995;14(7):1552-60.
Alcamí, J., Laín de Lera, T., Folgueira, L., Pedraza, M. A., Jacqué, J. M., Bachelerie, F., ... Gaynor, R. B. (1995). Absolute dependence on kappa B responsive elements for initiation and Tat-mediated amplification of HIV transcription in blood CD4 T lymphocytes. The EMBO Journal, 14(7), pp. 1552-60.
Alcamí J, et al. Absolute Dependence On Kappa B Responsive Elements for Initiation and Tat-mediated Amplification of HIV Transcription in Blood CD4 T Lymphocytes. EMBO J. 1995 Apr 3;14(7):1552-60. PubMed PMID: 7729429.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Absolute dependence on kappa B responsive elements for initiation and Tat-mediated amplification of HIV transcription in blood CD4 T lymphocytes. A1 - Alcamí,J, AU - Laín de Lera,T, AU - Folgueira,L, AU - Pedraza,M A, AU - Jacqué,J M, AU - Bachelerie,F, AU - Noriega,A R, AU - Hay,R T, AU - Harrich,D, AU - Gaynor,R B, PY - 1995/4/3/pubmed PY - 1995/4/3/medline PY - 1995/4/3/entrez SP - 1552 EP - 60 JF - The EMBO journal JO - EMBO J. VL - 14 IS - 7 N2 - The role of NF-kappa B-dependent signals in activating the transcriptional activity of the HIV regulatory region (LTR) was analyzed by systematic comparison of HIV LTR activity in human CD4 T cells purified from peripheral blood and a transformed lymphoblastoid T cell line. In normal CD4 T cells we also analyzed the role played by the viral kappa B responsive elements in HIV replication. Analysis of nuclear extracts of resting, normal T lymphocytes revealed the presence of the p50, but not the p65, NF-kappa B subunit and the induction by phorbol esters of bona fide (p50-p65) NF-kappa B complexes. In parallel, we observed clear enhancer-dependent HIV LTR transactivation comparable in intensity with that observed in lymphoblastoid cells. We show that unstimulated CD4 T lymphocytes offer a cellular environment of very low permissivity to HIV LTR functioning. This was in sharp contrast to the high spontaneous LTR activity observed in lymphoblastoid T cells, where LTR activity was essentially independent of kappa B-responsive elements. Due to the low basal LTR activity in resting T lymphocytes, NF-kappa B-dependent transactivation was a sine qua non event for induction of the HIV LTR. Surprisingly, even the function of HIV Tat in resting CD4 T lymphocytes was found to be absolutely dependent on LTR kappa B responsive elements. The relevance of these observations obtained in transient transfections was confirmed by the incapacity of blood CD4 T lymphocytes infected with an HIV infectious provirus carrying critical point mutations in the kappa B responsive elements to show any detectable transcriptional activity upon cell activation and prolonged culture in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0261-4189 UR - https://www.unboundmedicine.com/medline/citation/7729429/Absolute_dependence_on_kappa_B_responsive_elements_for_initiation_and_Tat_mediated_amplification_of_HIV_transcription_in_blood_CD4_T_lymphocytes_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0261-4189&date=1995&volume=14&issue=7&spage=1552 DB - PRIME DP - Unbound Medicine ER -