Abstract

The overall goal of these studies is to gain further insight into the role of second receptors during primate immunodeficiency virus entry into cells. The experimental goals are broken down into four categories. In the first set of experiments, the interaction between HIV-1 gp120 and various second receptors will be studied. These studies involve extensive mutagenesis of gp120, CKR5 and fusin.
The second Aim i s to clone and characterize the second receptors for HIV-2 and non human primate immunodeficiency viruses from chimpanzee, macaque and mangabey as well as from human PBMC.
The third Aim will evaluate the ability of HIV strains from different subtypes to utilize different second receptors.
The fourth Aim i s to understand whether and how variation in the second receptor expression patterns in macrophages and lymphocytes influences HIV-1 entry into these cells; variations in the sensitivity of infection to blocking by b-chemokines will also be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041420-02
Application #
2673010
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1997-07-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Aaron Diamond AIDS Research Center
Department
Type
DUNS #
786658872
City
New York
State
NY
Country
United States
Zip Code
10016

  Publications

Pugach, Pavel; Ozorowski, Gabriel; Cupo, Albert et al. (2015) A native-like SOSIP.664 trimer based on an HIV-1 subtype B env gene. J Virol 89:3380-95
Guttman, Miklos; Garcia, Natalie K; Cupo, Albert et al. (2014) CD4-induced activation in a soluble HIV-1 Env trimer. Structure 22:974-84
Berro, Reem; Yasmeen, Anila; Abrol, Ravinder et al. (2013) Use of G-protein-coupled and -uncoupled CCR5 receptors by CCR5 inhibitor-resistant and -sensitive human immunodeficiency virus type 1 variants. J Virol 87:6569-81
Klasse, P J (2013) Structural biology. A new bundle of prospects for blocking HIV-1 entry. Science 341:1347-8
Parker, Zahra F; Iyer, Shilpa S; Wilen, Craig B et al. (2013) Transmitted/founder and chronic HIV-1 envelope proteins are distinguished by differential utilization of CCR5. J Virol 87:2401-11
Berro, Reem; Klasse, Per Johan; Jakobsen, Martin R et al. (2012) V3 determinants of HIV-1 escape from the CCR5 inhibitors Maraviroc and Vicriviroc. Virology 427:158-65
Klasse, Per Johan (2012) The molecular basis of HIV entry. Cell Microbiol 14:1183-92
Anastassopoulou, Cleo G; Ketas, Thomas J; Sanders, Rogier W et al. (2012) Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Virology 428:86-97
Henrich, Timothy J; Lewine, Nicolas R P; Lee, Sun-Hee et al. (2012) Differential use of CCR5 by HIV-1 clinical isolates resistant to small-molecule CCR5 antagonists. Antimicrob Agents Chemother 56:1931-5
Berro, Reem; Klasse, Per Johan; Lascano, Danny et al. (2011) Multiple CCR5 conformations on the cell surface are used differentially by human immunodeficiency viruses resistant or sensitive to CCR5 inhibitors. J Virol 85:8227-40

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