Cellular regulators of infectious agents and methods of use

Abstract

A method of identifying a compound that modulates the activity of a cellular regulator is provided. The method consists of contacting a sample containing a cellular regulator and a nucleic acid element acted on by the cellular regulator with a test compound under conditions that allow replication or expression of the nucleic acid element or a gene or MRNA operatively linked to the nucleic acid element or gene, and an increase or decrease in the amount of replication or expression in the presence of the test compound compared to the absence of the test compound indicates that the compound has cellular regulator modulatory activity. A method of treating a HCV infection is also provided.

1 . A method of identifying a compound that modulates the activity of a cellular regulator comprising, contacting a sample containing a cellular regulator and a nucleic acid element acted on by the cellular regulator with a test compound under conditions that allow replication or expression of the nucleic acid element or a gene operatively linked to the nucleic acid element, and measuring the amount of replication or expression of the nucleic acid element or gene, an increase or decrease in the amount of replication or expression in the presence of the test compound compared to the absence of the test compound indicates that the compound has cellular regulator modulatory activity wherein said cellular regulator is a proteasome alpha subunit and said nucleic acid element is an internal ribosome entry site (IRES).  
     
     
         2 . The method of  claim 1 , wherein said proteosome alpha subunit is PSMA7.  
     
     
         3 . The method of  claim 1 , wherein said proteosome alpha subunit is encoded by a sequence comprising any of SEQ ID NOs: 127-139.  
     
     
         4 . The method of  claim 1 , wherein said test compound decreases the amount of replication or expression of said nucleic acid element or gene, thereby exhibiting cellular regulator inhibitory activity.  
     
     
         5 . The method of  claim 1 , wherein said test compound increases the amount of replication or expression of said nucleic acid element or gene, thereby exhibiting cellular regulator enhancing activity.  
     
     
         6 . The method of  claim 1 , wherein said nucleic acid element is a viral IRES.  
     
     
         7 . The method of  claim 1 , wherein said nucleic acid element is hepatitis C virus Ires.