Cellular Targets for Treatment of Retroviral Infection

Abstract

Cellular targets for anti-retroviral drug development are disclosed. The cellular targets comprise ATR kinase and its relevant substrates, based on the identification of the ATR kinase as required for the final step of retroviral DNA integration. Assays for identifying modulators of retroviral integration via the ATR kinase pathway are disclosed, as well as modulators identified by such assays. Pharmaceutical preparations and methods of their use in treating retroviral infection are also disclosed.

1 - 7 . (canceled) 
     
     
         8 . A method of interfering with retroviral replication in a host cell infected with the retrovirus, comprising inhibiting an constituent of the host cell needed to repair nucleic acids during retroviral DNA integration into the host cell genome, wherein the constituent is ATR kinase or a downstream target of ATR kinase. 
     
     
         9 . The method of  claim 8 , wherein the host cell is a human cell. 
     
     
         10 . The method of  claim 8 , wherein the host cell is a non-human cell. 
     
     
         11 . The method of  claim 8 , wherein the inhibiting is accomplished by exposing the cell to an agent that inhibits production or activity of ATR kinase or a downstream target of ATR kinase. 
     
     
         12 . The method of  claim 11 , wherein the agent is a methylxanthine 
     
     
         13 . The method of  claim 12 , wherein the methylxanthine is caffeine, paraxanthine, theobromine, theophylline, or metabolites or derivatives thereof. 
     
     
         14 . The method of  claim 8 , wherein the retrovirus is human immunodeficiency virus (HIV) or human T-cell leukemia virus (HTLV). 
     
     
         15 - 25 . (canceled)