This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Roulston, A Articles by Hiscott, J Search for Related Content PubMed PubMed Citation Articles by Roulston, A Articles by Hiscott, J

Chronic human immunodeficiency virus type 1 infection stimulates distinct NF-kappa B/rel DNA binding activities in myelomonoblastic cells.

Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.

ABSTRACT

The relationship between human immunodeficiency virus type 1 (HIV-1) infection and the induction of NF-kappa B binding activity was examined in a myeloid cell model of HIV-1 infection derived from the PLB-985 cell line. Chronic infection of PLB-985 cells led to increased monocyte-specific surface marker expression, increased c-fms gene transcription, and morphological alterations consistent with differentiation along the monocytic pathway. PLB-IIIB cells displayed a constitutive NF-kappa B-like binding activity that was distinct from that induced by tumor necrosis factor alpha or phorbol 12-myristate 13-acetate treatment of the parental PLB-985 cell line. This unique DNA binding activity consisted of proteins of 70, 90, and 100 kDa with a high degree of binding specificity for the NF-kappa B site within the PRDII domain of beta interferon. In this report, we characterize the nature of these proteins and demonstrate that binding of these proteins is also induced following Sendai paramyxovirus infection. The 70-kDa protein corresponds to the NF-kappa B RelA (p65) subunit, which is activated in response to an acute paramyxovirus infection or a chronic HIV-1 infection. Virus infection does not appear to alter the amount of RelA (p65) or NFKB1 (p50) but rather affects the capacity of I kappa B alpha to sequester RelA (p65), therefore leading to constitutive levels of RelA DNA binding activity and to increased levels of NF-kappa B-dependent gene activity. The virally induced 90- to 100-kDa proteins have a distinct binding specificity for the PRDII domain and an AT-rich sequence but do not cross-react with NF-kappa B subunit-specific antisera directed against NFKB1 (p105 or p50), NFKB2 (p100 or p52), RelA (p65), or c-rel. DNA binding of the 90- to 100-kDa proteins was not inhibited by recombinant I kappa B alpha/MAD-3 and was resistant to tryptic digestion, suggesting that these proteins may not be NF-kappa B related. Transient cotransfection experiments demonstrated that RelA and NFKB1 expression maximally stimulated HIV-1 LTR- and NF-kappa B-dependent reporter genes; differences in NF-kappa B-like binding activity were also reflected in higher constitutive levels of NF-kappa B-regulated gene expression in HIV-1-infected myeloid cells.

This article has been cited by other articles:

• Zhang, M., Drenkow, J., Lankford, C. S. R., Frucht, D. M., Rabin, R. L., Gingeras, T. R., Venkateshan, C., Schwartzkopff, F., Clouse, K. A., Dayton, A. I. (2006). HIV regulation of the IL-7R: a viral mechanism for enhancing HIV-1 replication in human macrophages in vitro. J. Leukoc. Biol. 79: 1328-1338 [Abstract] [Full Text]  
• Asin, S., Bren, G. D., Carmona, E. M., Solan, N. J., Paya, C. V. (2001). NF-kappa B cis-Acting Motifs of the Human Immunodeficiency Virus (HIV) Long Terminal Repeat Regulate HIV Transcription in Human Macrophages. J. Virol. 75: 11408-11416 [Abstract] [Full Text]  
• Lim, S. P., Garzino-Demo, A. (2000). The Human Immunodeficiency Virus Type 1 Tat Protein Up-Regulates the Promoter Activity of the Beta-Chemokine Monocyte Chemoattractant Protein 1 in the Human Astrocytoma Cell Line U-87 MG: Role of SP-1, AP-1, and NF-kappa B Consensus Sites. J. Virol. 74: 1632-1640 [Abstract] [Full Text]  
• DeLuca, C., Petropoulos, L., Zmeureanu, D., Hiscott, J. (1999). Nuclear Ikappa Bbeta Maintains Persistent NF-kappa B Activation in HIV-1-infected Myeloid Cells. J. Biol. Chem. 274: 13010-13016 [Abstract] [Full Text]  
• Kwon, H., Pelletier, N., DeLuca, C., Genin, P., Cisternas, S., Lin, R., Wainberg, M. A., Hiscott, J. (1998). Inducible Expression of Ikappa Balpha Repressor Mutants Interferes with NF-kappa B Activity and HIV-1 Replication in Jurkat T Cells. J. Biol. Chem. 273: 7431-7440 [Abstract] [Full Text]  
• Lokuta, M. A., Maher, J., Noe, K. H., Pitha, P. M., Shin, M. L., Shin, H. S. (1996). Mechanisms of Murine RANTES Chemokine Gene Induction by Newcastle Disease Virus. J. Biol. Chem. 271: 13731-13738 [Abstract] [Full Text]  
• Beauparlant, P., Lin, R., Hiscott, J. (1996). The Role of the C-terminal Domain of IkappaBalpha in Protein Degradation and Stabilization. J. Biol. Chem. 271: 10690-10696 [Abstract] [Full Text]