We have studied the mechanism of action of the HIV-1 Tat, HTLV-I Tax, and HTLV-l Rex proteins. We have made the following salient observations: 1) HIV-1 Tat acts as a transcriptional trans-activator of LTR-directed expression. Tat uses a bipartite target that includes both a nascent RNA and specific DNA elements within the LTR promoter. 2) The HIV-2 Tat protein acts like HIV-1 Tat, except that it requires a duplicated TAR RNA secondary structure for optimal activity. 3) A cellular protein that binds with specificity to the HIV-1 TAR RNA appears to be a general transcriptional factor. 4) HTLV-I Tax has pleiotropic up- and down-regulatory activities. Multiple protein domains within Tax are apparently necessary to mediate these diverse functions. 5) A novel transcriptional function for HTLV-I Rex has been observed. Our current understanding is that modulation of the HIV-l/HTLV-I LTR is mediated through complex interactions between cellular transcription factors and the viral trans-regulatory proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000547-01
Application #
3809714
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
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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