HIV Molecular Biology and Pathogenic Mechanisms of AIDS

Pavlakis, George N.

Abstract

This project aims to understand the role and mechanism of function of HIV regulation in the virus life cycle and disease development; and to dissect the mechanisms of nucleocytoplasmic trafficking of macromolecules. The conclusions of this work are also applied towards the design of better vaccine approaches against AIDS. We have focused our studies in this period on the interactions of Rev and Vpr with cellular components; and on the further understanding of posttranscriptional regulation and nucleocytoplasmic export, which are important steps in the process of gene expression. Our results contribute significantly to the further understanding of the basic mechanisms of nucleocytoplasmic traffic of macromolecules. The understanding of the regulatory mechanisms of HIV gene expression has many important practical applications. We have applied this knowledge to the development of improved DNA vaccination approaches.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: Division of Basic Sciences - NCI (NCI)
• Type: Intramural Research (Z01)
• Project #: 1Z01BC010750-01
• Application #: 7338798
• Study Section: Vector Biology Study Section (VB)
• Support Year: 1
• Fiscal Year: 2006

Institution

• Name: Basic Sciences
• Country: United States

Publications

Bergamaschi, Cristina; Jalah, Rashmi; Kulkarni, Viraj et al. (2009) Secretion and biological activity of short signal peptide IL-15 is chaperoned by IL-15 receptor alpha in vivo. J Immunol 183:3064-72

Uranishi, Hiroaki; Zolotukhin, Andrei S; Lindtner, Susan et al. (2009) The RNA-binding motif protein 15B (RBM15B/OTT3) acts as cofactor of the nuclear export receptor NXF1. J Biol Chem 284:26106-16

Felber, Barbara K; Zolotukhin, Andrei S; Pavlakis, George N (2007) Posttranscriptional control of HIV-1 and other retroviruses and its practical applications. Adv Pharmacol 55:161-97

Gragerov, Alexander; Horie, Kyoji; Pavlova, Maria et al. (2007) Large-scale, saturating insertional mutagenesis of the mouse genome. Proc Natl Acad Sci U S A 104:14406-11

Lindtner, Susan; Zolotukhin, Andrei S; Uranishi, Hiroaki et al. (2006) RNA-binding motif protein 15 binds to the RNA transport element RTE and provides a direct link to the NXF1 export pathway. J Biol Chem 281:36915-28

von Gegerfelt, Agneta S; Alicea, Candido; Valentin, Antonio et al. (2006) Long lasting control and lack of pathogenicity of the attenuated Rev-independent SIV in rhesus macaques. AIDS Res Hum Retroviruses 22:516-28

Smulevitch, Sergey; Bear, Jenifer; Alicea, Candido et al. (2006) RTE and CTE mRNA export elements synergistically increase expression of unstable, Rev-dependent HIV and SIV mRNAs. Retrovirology 3:6

Daelemans, Dirk; Costes, Sylvain V; Lockett, Stephen et al. (2005) Kinetic and molecular analysis of nuclear export factor CRM1 association with its cargo in vivo. Mol Cell Biol 25:728-39

Yuste, Eloisa; Johnson, Welkin; Pavlakis, George N et al. (2005) Virion envelope content, infectivity, and neutralization sensitivity of simian immunodeficiency virus. J Virol 79:12455-63

Kutzler, Michele A; Robinson, Tara M; Chattergoon, Michael A et al. (2005) Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J Immunol 175:112-23