Strategies of viral multi-functional regulator proteins

In order to replicate viruses have evolved a panoply of mechanisms to overcome and, in many cases utilize components of complex host pathways. In order to successfully orchestrate the cellular environment for the support of viral infection and replication and based on their inherently small genome sizes many viruses have adopted approaches that incorporate multiple functions into single proteins. In this application we propose to study mechanisms by which the adeno-associated virus Rep protein can regulate its many activities.

In order to productively replicate viruses have evolved a panoply of mechanisms to overcome and, in many cases utilize components of complex host pathways. In order to successfully orchestrate the cellular environment for the support of viral replication and based on their inherently limited genome sizes many viruses have adopted approaches that incorporate multiple functions into single proteins. This application aims to dissect the molecular bases for the coordination of the multiple functions that the Rep protein from the human adeno-associated virus (AAV) utilizes in order to support its complex lifestyle. Furthermore, this application is a component of a collaboration with a US laboratory that has recently been funded to determine the structures and biophysical characteristics of AAV Rep complexes. Our UK component outlined here aims at dissecting the functional relevance of these complexes within the context of the viral life cycle.