Abstract

Vpr and Vpx arose by an ancestral recombination event, and confer diverse properties upon primate lentiviruses, including the ability to replicate in quiescent cells. Vpr and Vpx are packaged into virions in amounts comparable to Gag proteins and mediate the transport of preintegration complexes into the nucleus of non-dividing cells. The current proposal is for continuation of studies of the novel packaging determinants of Vpr and Vpx, dissection of the preintegration complex transport mechanisms, and exploration of interactive cellular proteins that may mediate these and other activities.
The specific aims address the following question: 1. What are the determinants of Vpr/x Packaging into Virions and how do they work? a. What are the sequence determinants in Vpx for Packaging? b. What are the sequence determinants in HIV-2 Gag for Vpx Packaging? c. What are the sequence determinants for HIV-2 Vpr Packaging? 2. What are the roles of Vpr/x in Preintegration Complex Transport into the Nucleus? a. What is the role of Vpr phosphorylation in nuclear transport? b. What determinants of HIV-1 Vpr regulate preintegration complex transport? c. What determinants of Vpx regulate preintegration transport? 3. What are the roles of Vpr/x Interactive Cellular Proteins in HIV Infection? a. What is the role of li interaction with Vpx? b. Are there other Vpx- interactive proteins, and do they interact with Vpr?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI036071-05
Application #
2886918
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Program Officer
Sarver, Nava
Project Start
1995-01-01
Project End
2002-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Kyei, George Boateng; Cheng, Xiaogang; Ramani, Rashmi et al. (2015) Cyclin L2 is a critical HIV dependency factor in macrophages that controls SAMHD1 abundance. Cell Host Microbe 17:98-106
Zhou, Y; Ratner, L (2001) A novel inducible expression system to study transdominant mutants of HIV-1 Vpr. Virology 287:133-42
Pancio, H A; Vander Heyden, N; Ratner, L (2000) The C-terminal proline-rich tail of human immunodeficiency virus type 2 Vpx is necessary for nuclear localization of the viral preintegration complex in nondividing cells. J Virol 74:6162-7
Popov, S; Rexach, M; Zybarth, G et al. (1998) Viral protein R regulates nuclear import of the HIV-1 pre-integration complex. EMBO J 17:909-17
Popov, S; Rexach, M; Ratner, L et al. (1998) Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex. J Biol Chem 273:13347-52
Garnier, L; Ratner, L; Rovinski, B et al. (1998) Particle size determinants in the human immunodeficiency virus type 1 Gag protein. J Virol 72:4667-77