Human immunodeficiency viruses, HIV-1 and HIV-2, are the etiologic agents of acquired immunodeficiency syndrome (AIDS) in humans. The HIV-1 and HIV-2 envelope glycoproteins, gp120 and gp41, are critical for the entry of these viruses into the target cell, mediating virus binding to the CD4 receptor and membrane fusion. The envelope glycoproteins are the major targets for neutralizing antibodies and are likely to represent an important component in HIV-1 and/or HIV-2 vaccines. The overall goal of this proposal is to achieve an atomic level of understanding of the structural biology associated with the envelope glycoproteins of the human immunodeficiency viruses and the related simian immunodeficiency viruses. The strategy that will be employed to achieve this goal is based upon approaches that have yielded X-ray quality crystals of a complex containing an HIV-1 gp120 fragment bound to soluble fragments of CD4 and a neutralizing antibody. The structure of this complex will be determined and analyzed in Specific Aim 1.
In Specific Aim 2, an attempt will be made to determine comparable structures for gp120 fragments derived from primary HIV-1 isolates in different clades.
Specific Aims 3 and 4 are directed at obtaining useful crystals of HIV-1 gp120 fragments containing the complete gp41-interactive region and soluble gp120-gp41 oligomers, respectively. An attempt will be made to extend these studies to the HIV-2/SIV envelope glycoproteins in Specific Aim 5.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI040895-01
Application #
2005450
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1996-12-15
Project End
2001-11-30
Budget Start
1996-12-15
Budget End
1997-11-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215
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