NF-KAPPA-B ACTIVATES THE HIV PROMOTER IN NEURONS

被引:84
作者
RATTNER, A [1 ]
KORNER, M [1 ]
WALKER, MD [1 ]
CITRI, Y [1 ]
机构
[1] WEIZMANN INST SCI,DEPT BIOCHEM,IL-76100 REHOVOT,ISRAEL
关键词
AIDS DEMENTIA COMPLEX; HIV TRANSCRIPTION; NF-ALEPH-B; NEURONS; PRIMARY CULTURES;
D O I
10.1002/j.1460-2075.1993.tb06110.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human immunodeficiency virus (HIV) infection of the brain leads to massive neuronal damage, resulting in the AIDS (acquired immunodeficiency syndrome) dementia complex (ADC). A recent study using transgenic mice indicates that neurons possess transcription factors capable of activating the HIV promoter. To identify these, we transfected two types of primary cultures of rat neurons with HIV promoter-reporter gene constructs. The two chiB regulatory sites in the HIV long terminal repeat (LTR) are shown to be essential for strong promoter activity. Two proteins present in neurons, BETA and an NF-chiB-like protein, can bind the chiB sites. These proteins are shown to belong to distinct families of transcription factors. Mutation analysis and transfection of a dominant negative NF-chiB mutant, indicate that the neuronal NF-chiB-like activity mediates HIV promoter activation. cDNA cloning, biochemical and immunological analyses indicate that neuronal NF-chiB is similar to NF-chiB of other tissues. Transfections of primary neuron cultures with an HIV promoter-beta-galactosidase construct show that within these cultures, neurons are indeed the cells that highly activate the HIV promoter. Thus, analogous to the situation in T-lymphocytes and macrophages, NF-chiB is an activator of HIV transcription in neurons.
引用
收藏
页码:4261 / 4267
页数:7
相关论文
共 43 条
[1]   HIV ENHANCER ACTIVITY PERPETUATED BY NF-KAPPA-B INDUCTION ON INFECTION OF MONOCYTES [J].
BACHELERIE, F ;
ALCAMI, J ;
ARENZANASEISDEDOS, F ;
VIRELIZIER, JL .
NATURE, 1991, 350 (6320) :709-712
[2]   I-KAPPA-B - A SPECIFIC INHIBITOR OF THE NF-KAPPA-B TRANSCRIPTION FACTOR [J].
BAEUERLE, PA ;
BALTIMORE, D .
SCIENCE, 1988, 242 (4878) :540-546
[3]   A LARGE PROTEIN CONTAINING ZINC FINGER DOMAINS BINDS TO RELATED SEQUENCE ELEMENTS IN THE ENHANCERS OF THE CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX AND KAPPA-IMMUNOGLOBULIN GENES [J].
BALDWIN, AS ;
LECLAIR, KP ;
SINGH, H ;
SHARP, PA .
MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (04) :1406-1414
[4]   NF-KAPPA-B AND RELATED PROTEINS - REL DORSAL HOMOLOGIES MEET ANKYRIN-LIKE REPEATS [J].
BLANK, V ;
KOURILSKY, P ;
ISRAEL, A .
TRENDS IN BIOCHEMICAL SCIENCES, 1992, 17 (04) :135-140
[5]   THE SAME INDUCIBLE NUCLEAR PROTEINS REGULATES MITOGEN ACTIVATION OF BOTH THE INTERLEUKIN-2 RECEPTOR-ALPHA GENE AND TYPE-1 HIV [J].
BOHNLEIN, E ;
LOWENTHAL, JW ;
SIEKEVITZ, M ;
BALLARD, DW ;
FRANZA, BR ;
GREENE, WC .
CELL, 1988, 53 (05) :827-836
[6]   MAP2 IS LOCALIZED TO THE DENDRITES OF HIPPOCAMPAL-NEURONS WHICH DEVELOP IN CULTURE [J].
CACERES, A ;
BANKER, G ;
STEWARD, O ;
BINDER, L ;
PAYNE, M .
DEVELOPMENTAL BRAIN RESEARCH, 1984, 13 (02) :314-318
[7]  
CORBOY JR, 1992, SCIENCE, V258, P1804, DOI 10.1126/science.1465618
[8]   ACCURATE TRANSCRIPTION INITIATION BY RNA POLYMERASE-II IN A SOLUBLE EXTRACT FROM ISOLATED MAMMALIAN NUCLEI [J].
DIGNAM, JD ;
LEBOVITZ, RM ;
ROEDER, RG .
NUCLEIC ACIDS RESEARCH, 1983, 11 (05) :1475-1489
[9]   HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 IN SPINAL CORDS OF ACQUIRED IMMUNODEFICIENCY SYNDROME PATIENTS WITH MYELOPATHY - EXPRESSION AND REPLICATION IN MACROPHAGES [J].
EILBOTT, DJ ;
PERESS, N ;
BURGER, H ;
LANEVE, D ;
ORENSTEIN, J ;
GENDELMAN, HE ;
SEIDMAN, R ;
WEISER, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (09) :3337-3341
[10]   A DNA-BINDING PROTEIN CONTAINING 2 WIDELY SEPARATED ZINC FINGER MOTIFS THAT RECOGNIZE THE SAME DNA-SEQUENCE [J].
FAN, CM ;
MANIATIS, T .
GENES & DEVELOPMENT, 1990, 4 (01) :29-42