The goal of the research performed in the Section on Viral Gene Regulation is to define the molecular mechanisms responsible for the replication of HIV and related retroviruses and to investigate the role of host proteins that block virus infection. These studies are critical for developing new strategies to combat the AIDS epidemic, which continues to be a global threat to human health. To investigate the individual steps in HIV-1 reverse transcription, a major target of HIV therapy, we have developed reconstituted model systems. Much of our work focuses on the viral nucleocapsid protein (NC), a nucleic acid chaperone that remodels nucleic acid structures so that the most thermodynamically stable conformations are formed—an activity that is critical for highly efficient and specific viral DNA synthesis. We are also investigating the mechanism of antiviral activity of two human cytidine deaminases, APOBEC3G (A3G) and APOBEC3A (A3A). In other studies, our efforts are directed toward understanding the function of the viral capsid protein (CA) in HIV-1 assembly and early postentry events during the course of virus replication in vivo.
- Mitra M, Hercík K, Byeon IJ, Ahn J, Hill S, Hinchee-Rodriguez K, Singer D, Byeon CH, Charlton LM, Nam G, Heidecker G, Gronenborn AM, Levin JG. Structural determinants of human APOBEC3A enzymatic and nucleic acid binding properties. Nucleic Acids Res. 2014;42(2):1095-110.
- Jiang J, Ablan SD, Derebail S, Hercík K, Soheilian F, Thomas JA, Tang S, Hewlett I, Nagashima K, Gorelick RJ, Freed EO, Levin JG. The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Virology. 2011;421(2):253-65.
- Levin JG, Guo J, Rouzina I, Musier-Forsyth K. Nucleic acid chaperone activity of HIV-1 nucleocapsid protein: critical role in reverse transcription and molecular mechanism. Prog Nucleic Acid Res Mol Biol. 2005;80:217-86.
- Wu T, Gorelick RJ, Levin JG. Selection of fully processed HIV-1 nucleocapsid protein is required for optimal nucleic acid chaperone activity in reverse transcription. Virus Res. 2014;193:52-64.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Microbiology and Infectious Diseases
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