The envelope glycoprotein of the acquired immune deficiency syndrome (AIDS) virus (also known as LAV, HTLVIII, ARV and HIV) is the major surface antigen against which the neutralizing antibodies are produced in patients infected with the virus. The protein plays a major role in the infection process by providing receptors binding site and by inducing syncytia formation and cytopathic killing of the infected cells. The molecular cloning of the AIDS proviral DNA contributed immensely in assigning the functions for individual genes that might have direct role in the pathogenesis of the virus. The genetically engineered env gene is shown to direct the synthesis of a precursor envelope glycoprotein that is processed and transported to the cell surface indicating the presence of topogenic sequences necessary for transport and targeting o the protein to the cell surface. The goal of this project is to delineate these functional domains involved in protein transport and define their specific role in protein sorting process. I would use cloned DNA encoding the envelope glycoprotein of ARV-2 and make specific mutations in the DNA encoding the carboxyl terminal cytoplasmic region, transmembrane anchor domain as well as the signal region. The mutated genes would be introduced into mammalian cells and the protein products analyzed as to their intracellular transport and localization. The specific deletions (100-130 aa) of the unusually long cytoplasmic region (150 aa) as well as the anchor domain would define the functions of these domains in the intracellular and cell surface transport. Similarly, deletions in the leader (signal) region would define the minimum sequence requirement for translocation and cleavage by signal peptidase. Thus, the mutational analysis of the specific domains of ARV-2 envelope glycoprotein would help elucidate their contribution in the intracellular sorting process.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI025009-06
Application #
3454221
Study Section
Special Emphasis Panel (SSS)
Project Start
1987-09-30
Project End
1993-08-31
Budget Start
1991-09-01
Budget End
1993-08-31
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Type
DUNS #
017730458
City
Cleveland
State
OH
Country
United States
Zip Code
44195