We have examined the complex interactions needed for generating an infectious virus. We showed that the mature capsid proteins from two different lentiviruses, HIV-1 and SIVmac, can assemble into the mature core of the infectious particle. Additionally, we quantified the amounts of functional nucleocapsid (NC) and p6 protein needed during HIV-1 infection, and determined the effects of treating HIV-1 with suboptimal concentrations of protease inhibitors on viral protein processing and RNA maturation. We will study the trafficking of HIV-1 macromolecules and assembly. Once exported from the nucleus, HIV-1 RNA needs to traffic to proper subcellular locations to be translated or packaged;similarly, the newly synthesized Gag needs to be targeted to the plasma membrane for virus assembly. Using our newly developed imaging tools, we will investigate the mechanisms used by HIV-1 RNA for transport in the cytoplasm. HIV-1 RNA traffics to the plasma membrane for assembly;we will investigate the properties of this targeting event, including whether monomeric or dimeric RNA is targeted during assembly and the dwell time of the RNA that stays near the plasma membrane. We will also investigate Gag and RNA targeting in polarized T cells and in viral synapses. These experiments will provide an understanding of aspects of HIV-1 replication that we currently know very little about and will allow us to better understand how HIV-1 uses the cellular machinery to traffic its macromolecules.[Corresponds to Hu Project 3 in the October 2011 site visit report of the HIV Drug Resistance Program]

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010506-10
Application #
8552717
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2012
Total Cost
$563,724
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Chen, Jianbo; Rahman, Sheikh Abdul; Nikolaitchik, Olga A et al. (2016) HIV-1 RNA genome dimerizes on the plasma membrane in the presence of Gag protein. Proc Natl Acad Sci U S A 113:E201-8
Sardo, Luca; Hatch, Steven C; Chen, Jianbo et al. (2015) Dynamics of HIV-1 RNA Near the Plasma Membrane during Virus Assembly. J Virol 89:10832-40
Kuzembayeva, Malika; Dilley, Kari; Sardo, Luca et al. (2014) Life of psi: How full-length HIV-1 RNAs become packaged genomes in the viral particles. Virology 454-455C:362-370
Burdick, Ryan; Smith, Jessica L; Chaipan, Chawaree et al. (2010) P body-associated protein Mov10 inhibits HIV-1 replication at multiple stages. J Virol 84:10241-53
Paprotka, Tobias; Venkatachari, Narasimhan J; Chaipan, Chawaree et al. (2010) Inhibition of xenotropic murine leukemia virus-related virus by APOBEC3 proteins and antiviral drugs. J Virol 84:5719-29
Friew, Yeshitila N; Boyko, Vitaly; Hu, Wei-Shau et al. (2009) Intracellular interactions between APOBEC3G, RNA, and HIV-1 Gag: APOBEC3G multimerization is dependent on its association with RNA. Retrovirology 6:56
Chen, Jianbo; Pathak, Vinay K; Peng, Weiqun et al. (2008) Capsid proteins from human immunodeficiency virus type 1 and simian immunodeficiency virus SIVmac can coassemble into mature cores of infectious viruses. J Virol 82:8253-61
Chukkapalli, Vineela; Hogue, Ian B; Boyko, Vitaly et al. (2008) Interaction between the human immunodeficiency virus type 1 Gag matrix domain and phosphatidylinositol-(4,5)-bisphosphate is essential for efficient gag membrane binding. J Virol 82:2405-17