Project Description

Mason-Pfizer monkey virus (MPMV)-based vectors are being considered human gene therapy. One of the key steps towards the development of such vectors is the identification of the molecular mechanisms underlying the MPMV gRNA packaging process. The precursor polypeptide Pr78Gag is the key player in the assembly of new viral particles as well as in the efficient selection and packaging of two copies of the gRNA into the virus particles. The overall goal of this proposal is to gain a better understanding of the MPMV gRNA packaging process by delineating the mechanism(s) involved in the initial recognition of the gRNA by Pr78Gag. Towards this end, a combination of in vitro biochemical and in vivo genetic approaches will be employed. Specifically, we will: i) express, purify, and characterize MPMV Pr78Gag, ii) identify and characterize Pr78Gag binding site(s) on the MPMV gRNA, iii) establish correlations between the Pr78Gag binding site(s) and gRNA packaging, and iv) establish structure-function relationships of purine-rich sequences during MPMV gRNA packaging.