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

Urano, Emiko; Kariya, Yumi; Futahashi, Yuko; Ichikawa, Reiko; Hamatake, Makiko; Fukazawa, Hidesuke; Morikawa, Yuko; Yoshida, Takeshi; Koyanagi, Yoshio; Yamamoto, Naoki; Komano, Jun

doi:10.1016/j.febslet.2008.10.047

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Volume 582, Issue 29 , Pages 4053-4058, 10 December 2008

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

Edited by Ivan Sadowski

Emiko Urano
- National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
- Graduate School of Infection Control Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan
Yumi Kariya
- National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
Yuko Futahashi
- National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
Reiko Ichikawa
- National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
Makiko Hamatake
- National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
Hidesuke Fukazawa
- Department of Bioactive Molecules, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
Yuko Morikawa
- Graduate School of Infection Control Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan
Takeshi Yoshida
- Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
Yoshio Koyanagi
- Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
Naoki Yamamoto
- National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
Jun Komano
- National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
- Corresponding author. Fax: +81 3 5285 5037.

Received 26 August 2008; received in revised form 10 October 2008; accepted 21 October 2008. published online 07 November 2008.

Abstract

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.

Keywords: HIV-1 replication, Host factor, cDNA library, Brd4, P-TEFb complex, Tat-dependent LTR transcription