Recipient Organization
IOWA STATE UNIVERSITY
S. AND 16TH ELWOOD
AMES,IA 50011
Performing Department
VETERINARY MEDICINE
Non Technical Summary
Rev is a regulatory protein essential for the replication of HIV and other lentiviruses. The long term goal of this research is to determine the structure of lentivirus Rev proteins. The objective of the proposed studies is to identify structures essential for Rev activity.
Animal Health Component
75%
Research Effort Categories
Basic
(N/A)
Applied
75%
Developmental
25%
Goals / Objectives
In all lentiviruses, the regulatory protein Rev is essential for virus replication. Rev functions to facilitate export of the incompletely spliced viral RNAs from the nucleus to the cytoplasm. It binds a structure in the viral pre-mRNA called the Rev-responsive element (RRE), multimerizes, then utilizes the CRM1 nuclear export pathway to redirect movement of incompletely spliced viral RNA out of the nucleus. Discrete functional domains within Rev mediate interaction with cellular proteins and viral RNA that are required for nuclear localization, RNA binding, multimerization, and nuclear export. The central premise of this proposal is that integrating computational and experimental approaches in a comparative analysis of Rev proteins from different lentiviruses will not only provide insights into critical structural features required for function, but will point to new strategies for generating a high-resolution structure of Rev.
Project Methods
Our hypothesis is that lentivirus Rev proteins, despite their lack of amino acid sequence similarity, share structural homologies that are required for Rev function. We propose a comparative approach that integrates computational and experimental methods to determine the structure of Rev.