The Molecular Virology Section focuses on basic and applied research on human retroviruses, HIV-1 and HTLV-I. The research program covers three 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 1995-1996 are summarized. 1) We have found that the HIV-1 Tat protein directly modulates the LTR-regulating activity of transcription factor Sp1. The mechanism of this modulation is a Tat-induced post-translational phosphorylation of Sp1 mediated through nuclear protein kinase, DNA-PK. 2) We have constructed recombinant HIV-1 genomes that permit the tissue culture selection of Tat mutations that either positively or negatively influence virus replication. Through this procedure, we have uncovered 26 new mutations in Tat. This approach has allowed us to distinguish between mutations that influence replication versus those that influence trans-activation. 3) A protein previously characterized by us as a TAR-RNA-binding protein (TRBP) has been delineated to be a suppressor of the interferon activated effector kinase (PKR). We found that TRBP potently represses the tumor-suppressor activity of PKR. Overexpression of TRBP produced transformation of NIH 3T3 cells. 4) We have developed Herpes Simplex virus thymidine kinase (TK) as a gain-of-function marker for HIV-1. HIV-1 engineered to express TK was shown to be effectively treated with ganciclovir (GCV). GCV-treatment resulted in efficient elimination of integrated copies of the HIV-1 provirus. 5) We have developed a physical model for the minimal catalytic domain of a hammerhead ribozyme. We have used the hammerhead ribozyme to develop an RNA virus vector system (Semliki forest virus) as an efficient vehicle for an anti-HIV-1 ribozyme. 6) Through the yeast two-hybrid assay approach, we have identified and characterized cDNAs that encode cellular proteins that bind to HTLV-I Tax. One of these cellular proteins is a regulator of a G-protein signaling cascade. A second protein is a mitotic checkpoint factor. The functions of both proteins agree with aspects of HTLV-I biology in cellular transformation.
| 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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