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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
Author(s) -
Urano Emiko,
Kariya Yumi,
Futahashi Yuko,
Ichikawa Reiko,
Hamatake Makiko,
Fukazawa Hidesuke,
Morikawa Yuko,
Yoshida Takeshi,
Koyanagi Yoshio,
Yamamoto Naoki,
Komano Jun
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.10.047
Subject(s) - brd4 , complementary dna , identification (biology) , cdna library , replication (statistics) , p tefb , biology , human immunodeficiency virus (hiv) , domain (mathematical analysis) , computational biology , microbiology and biotechnology , chemistry , virology , genetics , bromodomain , dna , gene , gene expression , histone , promoter , mathematical analysis , botany , mathematics
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.
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