Abstract

The goal of this proposal is to more fully understand the role of the Gag proteins in the assembly of HIV-1 virions, with an emphasis on understanding the biochemical basis of infectivity-inactivating amino acid substitutions. In particular, the primary sequence requirements for Gag multimerization will be determined, studying both HIV-1 and also other members of the immunodeficiency virus family. The role of viral RNA in Gag multimerization will also be studied. Finally, a selection of techniques will be used to assess how mutations affecting Gag multimerization impact upon HIV-1 infectivity in vitro.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041857-02
Application #
2673091
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1997-09-01
Project End
2001-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032

  Publications

Gurer, Cagan; Hoglund, Anders; Hoglund, Stefan et al. (2005) ATPgammaS disrupts human immunodeficiency virus type 1 virion core integrity. J Virol 79:5557-67
Gurer, Cagan; Berthoux, Lionel; Luban, Jeremy (2005) Covalent modification of human immunodeficiency virus type 1 p6 by SUMO-1. J Virol 79:910-7
Chang, Fred; Re, Fabio; Sebastian, Sarah et al. (2004) HIV-1 Vpr induces defects in mitosis, cytokinesis, nuclear structure, and centrosomes. Mol Biol Cell 15:1793-801
Gurer, Cagan; Cimarelli, Andrea; Luban, Jeremy (2002) Specific incorporation of heat shock protein 70 family members into primate lentiviral virions. J Virol 76:4666-70
Cimarelli, A; Luban, J (2001) Context-dependent phenotype of a human immunodeficiency virus type 1 nucleocapsid mutation. J Virol 75:7193-7
Cimarelli, A; Sandin, S; Hoglund, S et al. (2000) Rescue of multiple viral functions by a second-site suppressor of a human immunodeficiency virus type 1 nucleocapsid mutation. J Virol 74:4273-83
Cimarelli, A; Luban, J (2000) Human immunodeficiency virus type 1 virion density is not determined by nucleocapsid basic residues. J Virol 74:6734-40
Cimarelli, A; Sandin, S; Hoglund, S et al. (2000) Basic residues in human immunodeficiency virus type 1 nucleocapsid promote virion assembly via interaction with RNA. J Virol 74:3046-57
Cimarelli, A; Luban, J (1999) Translation elongation factor 1-alpha interacts specifically with the human immunodeficiency virus type 1 Gag polyprotein. J Virol 73:5388-401
Burniston, M T; Cimarelli, A; Colgan, J et al. (1999) Human immunodeficiency virus type 1 Gag polyprotein multimerization requires the nucleocapsid domain and RNA and is promoted by the capsid-dimer interface and the basic region of matrix protein. J Virol 73:8527-40