Detection of viral infection

Abstract

The present invention relates to methods of detecting an increased likelihood of virus infection in a subject. In particular, the present invention relates to methods of detecting an increased likelihood of virus infection in a subject by detecting an altered level of at least one microRNA (miRNA), as well as methods of treating or preventing virus infection. The present invention also relates to nucleotide arrays, oligonucleotides and kits useful for the detection of miRNAs associated with an increased likelihood of virus infection in a subject.

1 . A method for determining the likelihood of virus infection in a subject, the method comprising determining the level of at least one miRNA associated with virus infection in the subject, wherein an altered level of the at least one miRNA in the subject when compared to a control is indicative of an increased likelihood of virus infection. 
     
     
         2 . The method of  claim 1 , wherein the virus is Henipavirus. 
     
     
         3 . The method of  claim 2 , wherein the Henipavirus virus is Hendra virus. 
     
     
         4 . The method of any one of  claims 1  to  3 , wherein the at least one miRNA includes a miRNA selected from miR-151-5p, miR-146a, miR-128, miR-140-3p, miR-100, miR-28-3p, miR-302c, miR-150 and/or miR142-3p. 
     
     
         5 . The method of any one of  claims 1  to  4 , wherein the level of the at least one miRNA is increased when compared to the control. 
     
     
         6 . The method of  claim 5 , wherein the at least one miRNA is selected from miR-146a, miR-150 and/or miR-142-3p. 
     
     
         7 . The method of  claim 6 , wherein the at least one miRNA is miR-146a. 
     
     
         8 . The method of any one of  claims 1  to  7 , wherein the method comprises determining the level of the at least one miRNA in a blood sample obtained from the subject. 
     
     
         9 . The method of any one of  claims 1  to  8 , wherein the method comprises amplifying the miRNA. 
     
     
         10 . The method of  claim 9 , wherein the miRNA is amplified by quantitative reverse transcription polymerase chain reaction. 
     
     
         11 . The method of any one of  claims 1  to  10 , wherein the subject is a human. 
     
     
         12 . The method of any one of  claims 1  to  10 , wherein the subject is a non-human animal. 
     
     
         13 . The method of  claim 12 , wherein the subject is a horse, pig, sheep, bovine, chicken, bat, dog or ferret. 
     
     
         14 . The method of any one of  claims 1  to  13 , wherein the method is performed before virus is detectable in a sample from the subject. 
     
     
         15 . The method of any one of  claims 1  to  14 , further comprising diagnosing virus infection in the subject. 
     
     
         16 . The method of  claim 15 , wherein diagnosing virus infection comprises detecting a viral polypeptide, viral polynucleotide, viral particle and/or antibody to a viral polypeptide in a subject sample. 
     
     
         17 . The method of  claim 16 , wherein diagnosing virus infection comprises performing ELISA, PCR, immunofluorescence assay, serum neutralisation test and/or virus isolation. 
     
     
         18 . A method of detecting virus replication in a biological sample obtained from a subject, the method comprising detecting in the sample a level of at least one miRNA associated with virus infection, wherein an altered level of the at least one miRNA in the sample when compared to a control is indicative of virus replication. 
     
     
         19 . The method of  claim 18 , wherein the at least one miRNA is selected from miR-151-5p, miR-146a, miR-128, miR-140-3p, miR-100, miR-28-3p, miR-302c, miR-150 and/or miR142-3p. 
     
     
         20 . A method of treatment comprising performing the method of any one of  claims 1  to  19  and administering a therapeutic agent for the treatment of virus infection or a symptom of virus infection. 
     
     
         21 . A nucleotide array for determining the likelihood of virus infection in a subject, the microarray comprising miRNA-specific probes for at least one miRNA associated with virus infection. 
     
     
         22 . The method of  claim 21 , wherein the miRNA is selected from miR-151-5p, miR-146a, miR-128, miR-140-3p, miR-100, miR-28-3p, miR-302c, miR-150 and/or miR142-3p. 
     
     
         23 . A set of oligonucleotides for amplifying at least one miRNA associated with virus replication, wherein the at least one miRNA is selected from miR-151-5p, miR-146a, miR-128, miR-140-3p, miR-100, miR-28-3p, miR-302c, miR-150 and/or miR142-3p. 
     
     
         24 . A kit comprising a nucleotide array for determining the likelihood of virus infection in a subject, the nucleotide array comprising miRNA-specific probes for at least one miRNA selected from miR-151-5p, miR-146a, miR-128, miR-140-3p, miR-100, miR-28-3p, miR-302c, miR-150 and/or miR142-3p. 
     
     
         25 . A kit comprising a set of oligonucleotides for amplifying at least one miRNA associated with virus replication, where the at least one miRNA is selected from miR-151-5p, miR-146a, miR-128, miR-140-3p, miR-100, miR-28-3p, miR-302c, miR-150 and/or miR142-3p. 
     
     
         26 . The kit of  claim 24  or  claim 25 , wherein the kit further comprises a control sample. 
     
     
         27 . A method of treating or preventing virus infection in a subject, the method comprising administering to the subject an antagonist of at least one miRNA associated with virus infection. 
     
     
         28 . The method of  claim 27 , wherein the at least one miRNA is selected from miR-151-5p, miR-146a, miR-128, miR-140-3p, miR-100, miR-28-3p, miR-302c, miR-150 and/or miR142-3p. 
     
     
         29 . The method of  claim 27  or  claim 28 , wherein the virus is Henipavirus. 
     
     
         30 . The method of  claim 29 , wherein the virus is Hendra virus. 
     
     
         31 . The method of any one of  claims 27  to  30 , wherein the antagonist is an oligonucleotide comprising a nucleotide sequence complementary to the miRNA. 
     
     
         32 . The method of any one of  claims 27  to  31 , wherein the subject is a human. 
     
     
         33 . The method of any one of  claims 27  to  31 , wherein the subject is non-human animal. 
     
     
         34 . The method of  claim 33 , wherein the subject is a horse, pig, sheep, bovine, chicken, bat, dog or ferret. 
     
     
         35 . The method of any one of  claims 27  to  34 , wherein the level of miRNA is increased during virus infection in the absence of the antagonist. 
     
     
         36 . The method of  claim 35 , wherein the miRNA is selected from miR-146a, miR-150 and/or miR-142-3p. 
     
     
         37 . The method of any one of  claims 27  to  36 , wherein the method comprises administering to the subject the antagonist of at least one miRNA associated with virus infection and an NF-κB inhibitor. 
     
     
         38 . The method of any one of  claims 27  to  37 , comprising performing the method of any one of  claims 1  to  19  prior to administering the antagonist to the subject. 
     
     
         39 . A method of treating or preventing virus infection in a subject, the method comprising administering to the subject an NF-κB inhibitor. 
     
     
         40 . Use of an antagonist of a miRNA associated with virus infection in the manufacture of a medicament for the treatment or prevention of virus infection. 
     
     
         41 . Use of an antagonist of a miRNA associated with virus infection and an NF-κB inhibitor in the manufacture of a medicament for the treatment or prevention of virus infection. 
     
     
         42 . An antagonist of a miRNA associated with virus infection for use in the treatment or prevention of virus infection. 
     
     
         43 . An antagonist of a miRNA associated with virus infection and an NF-κB inhibitor for use in the treatment or prevention of virus infection. 
     
     
         44 . A pharmaceutical composition comprising an antagonist of a miRNA associated with virus infection and a pharmaceutically acceptable carrier or excipient. 
     
     
         45 . The pharmaceutical composition of  claim 44  further comprising an NF-κB inhibitor. 
     
     
         46 . The use of  claim 40  or  41 , the antagonist of  claim 42  or  43 , or the pharmaceutical composition of  claim 44  or  45 , wherein the virus is Henipavirus.