Identification of the P-TEFb complex-interacting domain of Brd4 as an inhibitor of HIV-1 replication by functional cDNA library screening in MT-4 cells.
We conducted a phenotypic cDNA screening using a T cell line-based assay to identify human genes that render cells resistant to human immunodeficiency virus type 1 (HIV-1). We isolated potential HIV-1 resistance genes, including the carboxy terminal domain (CTD) of bromodomain-containing protein 4 (Brd4). Expression of GFP-Brd4-CTD was tolerated in MT-4 and Jurkat cells in which HIV-1 replication was markedly inhibited. We provide direct experimental data demonstrating that Brd4-CTD serves as a specific inhibitor of HIV-1 replication in T cells. Our method is a powerful tool for the identification of host factors that regulate HIV-1 replication in T cells.
Urano
Emiko
E
National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Kariya
Yumi
Y
Futahashi
Yuko
Y
Ichikawa
Reiko
R
Hamatake
Makiko
M
Fukazawa
Hidesuke
H
Morikawa
Yuko
Y
Yoshida
Takeshi
T
Koyanagi
Yoshio
Y
Yamamoto
Naoki
N
Komano
Jun
J
D001681:Biological Assay; D018797:Cell Cycle Proteins; D002460:Cell Line; D015723:Gene Library; D017930:Genes, Reporter; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000276:immunology*; D000092468:Bromodomain Containing Proteins
D018797:Cell Cycle Proteins; D008156:Luciferases; D009687:Nuclear Proteins; D042925:Positive Transcriptional Elongation Factor B; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins