We have studied the mechanisms by which HIV-1 Tat and HTLV-I Tax proteins activate transcription. Recent finding relevant to the HIV-1 system include the following: 1) We have obtained evidence that Tat functions as a transcriptional adaptor that indirectly activates the HIV-1 LTR only in the setting of upstream """"""""enhancers."""""""" 2) We have implicated a novel non-transcriptional function in Tat that influences HIV-1 infectivity. 3) We have determined that differences in the basic RNA-binding domains of HIV-1 Tat and HIV-2 Tat confer type specific transactivation of the respective LTRs. 4) We have defined the RNA-binding domain of a TAR-RNA- binding protein TRBP, which categorizes this protein into the family of RNA-binding proteins that includes human dsI kinase and Drosophila Staufen. For the HTLV-I system, recent accomplishments include: 1) the demonstration that HTLV-I Tax protein induces the formation of micro- nuclei in mammalian cells. 2) The characterization of an activation domain and a targetting domain in Tax. A third area of interest for the laboratory is the study of ribozymes. We have constructed five different ribozymes each targetted to an independent locus in the HIV-1 genome. We have also made transgenic mice that contain ribozyme-genes which direct synthesis of ribozymes capable of cleaving HIV-1 RNAs. Ongoing studies in the laboratory have also delineated that ribozymes can be used as thermal stable enzymes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000547-04
Application #
3768833
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
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
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
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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