Reciprocal modulation of transcriptional activities between HIV-1 Tat and MHC class II transactivator CIITA.
HIV-1 is the etiologic agent of acquired immune deficiency syndrome (AIDS). Functional loss of antigen-presenting cells (APC) in HIV-1 infection is considered to be involved in AIDS pathogenesis. We found that actions of the viral transactivator Tat and the transactivator of MHC class II genes, CIITA, are mutually inhibitory. While Tat inhibited expression of MHC class II genes in APC, overexpression of CIITA inhibited Tat and subsequently HIV-1 replication. This action of Tat appears to be mediated by sequestering the common cofactor, cyclin T1, but not p300 and CBP. These reciprocal actions between Tat and CIITA not only explains the functional impairment of APC in HIV-1 infection but also rationalizes the suppression of HIV-1 virus load by induction of CIITA such as IFN-gamma.
Okamoto
H
H
Department of Molecular Genetics, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan.
Asamitsu
K
K
Nishimura
H
H
Kamatani
N
N
Okamoto
T
T
D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D056906:Cyclin T; D016213:Cyclins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D005802:Genes, MHC Class II; D017930:Genes, Reporter; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009687:Nuclear Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
C503684:CCNT1 protein, human; D056906:Cyclin T; D016213:Cyclins; D015696:Gene Products, tat; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D054322:tat Gene Products, Human Immunodeficiency Virus; D015500:Chloramphenicol O-Acetyltransferase