Assay and medicament

Abstract

The invention relates to defective interfering viruses and defective interfering virus RNAs that are effective as antiviral agents. The invention also relates to methods for identifying defective interfering virus RNAs that can be used as effective antiviral agents.

1 . A defective interfering virus RNA, wherein the RNA is mutated to prevent expression of any encoded protein. 
     
     
         2 . The DI virus RNA of  claim 1 , wherein one or more AUG initiation codons are mutated. 
     
     
         3 . The DI virus RNA of  claim 2 , wherein all the AUG initiation codons are mutated. 
     
     
         4 . The DI virus RNA of  claim 2 , wherein one or more AUG are mutated to AUC. 
     
     
         5 . The DI virus RNA of  claim 1 , wherein the DI virus is 1/244. 
     
     
         6 . A DI virus which comprises the DI virus RNA  claim 1 . 
     
     
         7 . A method of treating or prophylaxis of influenza A infection, comprising administering to the patient a therapeutically effective amount of the DI virus according to  claim 6 . 
     
     
         8 . A method to identify an antiviral agent comprising monitoring for the production of RNA from segments 1, 2 and 3 of influenza A virus in the presence of a test defective interfering influenza virus RNA, wherein a defective interfering virus RNA that interferes with production of RNA from each of segment 1, 2 and 3 is identified as an antiviral agent. 
     
     
         9 . The method of  claim 8 , wherein the method is conducted in a host cell. 
     
     
         10 . The method of  claim 9 , wherein the host cell is transfected with nucleic acid comprising segments 1, 2 and 3 of influenza virus. 
     
     
         11 . The method of  claim 10 , wherein each of said segments 1, 2 and 3 is provided on a separate plasmid. 
     
     
         12 . The method of  claim 8 , wherein RNA production from each of segments 1, 2 and 3 is monitored in a separate assay. 
     
     
         13 . The method of  claim 8 , wherein the RNA comprises cRNA, mRNA and/or vRNA. 
     
     
         14 . The method of  claim 13 , wherein both cRNA and mRNA production are monitored. 
     
     
         15 . The method according to  claim 8 , wherein one or more of segments 1, 2 or 3 is provided as a construct with an encoded reporter gene, such that a reduction in production of RNA from the segment reduces expression of the reporter gene. 
     
     
         16 . An antiviral agent identified by the method of  claim 8  for use in a method of treatment or prophylaxis of influenza A infection. 
     
     
         17 . A cloned or recombinant defective interfering influenza A virus comprising RNA derived from segment 1, 2 or 3, wherein said RNA comprises:
 (a) an RNA of between 300 to 600 nucleotides in length;   (b) at least 100 nucleotides from the 5′ and 3′ ends of segment 1, 2 or 3;   (c) a central deletion of nucleotides of said segment;   wherein said defective interfering influenza virus is capable of interfering with RNA production from segments 1, 2 and 3 of influenza A.   
     
     
         18 . The defective interfering virus of  claim 17 , wherein the DI virus is not 1/244. 
     
     
         19 . The defective interfering virus of  claim 17 , for use in a method of treatment or prophylaxis of influenza A infection.