During the process of HIV replication two viral RNAs are encapsidated into the assembling virus particle where they are found in stable but non- covalent association. Following infection of cells the RNA is converted into DNA via reverse transcription. The long term objective of this program is to understand in molecular detail the steps that result in vivo ecapsidation and dimer formation, and to understand how the structure and organization of the viral RNA influence reverse transcription. A combination of approaches are proposed to investigate RNA encapsidation, RNA dimer formation, RNA organization, and minus strand DNA synthesis during reverse transcription. We will attempt to (1) elucidate the higher order structure of the encapsidation region, (2) understand the mature of the primary dimer linkage site, 93) determine how lack of correct dimer formation leads to abrogation of replication, (4) characterize the role of nucleocapsid protein in replication and, (5) test the hypothesis that juxtaposition of the 5' and 3' ends of the RNA template are required for minus strand DNA synthesis. We hope to develop a comprehensive picture that helps us understand in and exact way how correct encapsidation and dimer formation lead to correct reverse transcription.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZRG5-ARRA (02))
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Plaeger, Susan F
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University of Wisconsin Madison
Internal Medicine/Medicine
Schools of Medicine
United States
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Sakuragi , J; Shioda, T; Panganiban, A T (2001) Duplication of the primary encapsidation and dimer linkage region of human immunodeficiency virus type 1 RNA results in the appearance of monomeric RNA in virions. J Virol 75:2557-65
Schwartz, M D; Fiore, D; Panganiban, A T (1997) Distinct functions and requirements for the Cys-His boxes of the human immunodeficiency virus type 1 nucleocapsid protein during RNA encapsidation and replication. J Virol 71:9295-305
McBride, M S; Schwartz, M D; Panganiban, A T (1997) Efficient encapsidation of human immunodeficiency virus type 1 vectors and further characterization of cis elements required for encapsidation. J Virol 71:4544-54
Sakuragi, J I; Panganiban, A T (1997) Human immunodeficiency virus type 1 RNA outside the primary encapsidation and dimer linkage region affects RNA dimer stability in vivo. J Virol 71:3250-4
Hoglund, S; Ohagen, A; Goncalves, J et al. (1997) Ultrastructure of HIV-1 genomic RNA. Virology 233:271-9
McBride, M S; Panganiban, A T (1997) Position dependence of functional hairpins important for human immunodeficiency virus type 1 RNA encapsidation in vivo. J Virol 71:2050-8
Casella, C R; Raffini, L J; Panganiban, A T (1997) Pleiotropic mutations in the HIV-1 matrix protein that affect diverse steps in replication. Virology 228:294-306
McBride, M S; Panganiban, A T (1996) The human immunodeficiency virus type 1 encapsidation site is a multipartite RNA element composed of functional hairpin structures. J Virol 70:2963-73