This project focuses on basic and applied research on human retroviruses, HIV-1 and HTLV-I. It covers three broad areas--I) basic research studying the regulated expression of HIV-1; II) basic research on cellular transformation events as related to HTLV-I; and III) applied research towards developing HIV-1-based vectors and designing molecular ribozymes targeted against HIV-1. Some notable scientific findings from our research program in 1997-1998 include: 1) the demonstration that Tat binds a histone acetylase and affects transcription of integrated LTR-promoters; 2) evidence that Tat can influence shut-off host cell protein synthesis by binding to EF-1d; 3) evidence that extracellular Tat protein antagonize CXCR4-receptor usage; 4) generation of an attenuated HIV-1 virus using IkB-a; 5) the characterization of mitotic checkpoint proteins HsMAD1 and HsMAD2 and their interactions with HTLV-I Tax in cellular transformation; 6) demonstration of Tax effects on G1 to S cell phase transition through modulation of cyclin D-cdk and p110RB; 7) the identification of a novel selenium containing protein; and 8) the generation of infectious HIV viral particles containing a therapeutic ribozyme. In the coming year, we plan to extend our findings into each of these research areas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000547-10
Application #
6098965
Study Section
Special Emphasis Panel (LMM)
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Yeung, Man Lung; Houzet, Laurent; Yedavalli, Venkat S R K et al. (2009) A genome-wide short hairpin RNA screening of jurkat T-cells for human proteins contributing to productive HIV-1 replication. J Biol Chem 284:19463-73
Yeung, Man Lung; Bennasser, Yamina; Watashi, Koichi et al. (2009) Pyrosequencing of small non-coding RNAs in HIV-1 infected cells: evidence for the processing of a viral-cellular double-stranded RNA hybrid. Nucleic Acids Res 37:6575-86
Grassmann, Ralph; Jeang, Kuan-Teh (2008) The roles of microRNAs in mammalian virus infection. Biochim Biophys Acta :
Jeang, Kuan-Teh (2007) World AIDS Day 2007: AIDS at 26, are we there yet? Retrovirology 4:86
Lee, Jia Hai; Yedavalli, Venkat Rk; Jeang, Kuan-Teh (2007) Activation of HIV-1 expression and replication by cGMP dependent protein kinase type 1-beta (PKG1beta). Retrovirology 4:91
Berkhout, Ben; Jeang, Kuan-Teh (2007) RISCy business: MicroRNAs, pathogenesis, and viruses. J Biol Chem 282:26641-5
Yeung, Man Lung; Bennasser, Yamina; Le, Shu-Yun et al. (2007) RNA interference and HIV-1. Adv Pharmacol 55:427-38
Yeung, Man Lung; Benkirane, Monsef; Jeang, Kuan-Teh (2007) Small non-coding RNAs, mammalian cells, and viruses: regulatory interactions? Retrovirology 4:74
Yedavalli, Venkat R K; Jeang, Kuan-Teh (2007) Methylation: a regulator of HIV-1 replication? Retrovirology 4:9
Triboulet, Robinson; Mari, Bernard; Lin, Yea-Lih et al. (2007) Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science 315:1579-82

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