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PMID: 8394446 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Journal of virology ·Vol. 67 ·No. 9 ·1993-09-00 ·Pages 5235-46

Roulston A, Beauparlant P, Rice N, Hiscott J

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.

Related Genes
c-fms rel
MeSH Terms
Base Sequence Binding Sites Cell Differentiation/drug effects DNA-Binding Proteins/biosynthesis Enhancer Elements, Genetic Gene Expression Regulation, Viral Genes, fms HIV-1/physiology Humans Interferon-beta/genetics Leukemia, Myeloid Molecular Sequence Data Monocytes/cytology,drug effects NF-kappa B/biosynthesis Oligodeoxyribonucleotides Parainfluenza Virus 1, Human/physiology Promoter Regions, Genetic Protein-Tyrosine Kinases/biosynthesis Proto-Oncogene Proteins/biosynthesis Proto-Oncogene Proteins c-rel Tetradecanoylphorbol Acetate/pharmacology Transcription, Genetic Tumor Cells, Cultured Tumor Necrosis Factor-alpha/pharmacology
Chemicals
DNA-Binding Proteins NF-kappa B Oligodeoxyribonucleotides Proto-Oncogene Proteins Proto-Oncogene Proteins c-rel Tumor Necrosis Factor-alpha Interferon-beta Protein-Tyrosine Kinases Tetradecanoylphorbol Acetate
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Roulston A
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
Beauparlant P
Rice N
Hiscott J
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.67.9.5235-5246.1993
Published
1993-09-00
Pages
5235-46
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC237921
Subset
IM
Grants
NCI NIH HHS · N01-CO-74101 · United States
External Links
PubMed source DOI: 10.1128/JVI.67.9.5235-5246.1993 PMC Full Text View journal details
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