Methods for the detection of jc polyoma virus

Abstract

Methods and compositions for determining whether a subject is at risk for PML, including subjects being treated with immunosuppressants, by determining whether the subject harbors a JCV variant with reduced binding for sialic acid relative to a normal JCV, are presented. Furthermore, combinations of JCV-VP1 sequence variations that are associated with PML and that can be used as a basis of an assay for identifying subjects susceptible to PML, subjects with PML (e.g., early stage PML), or subjects at risk of developing PML in response to an immunosuppressive treatment are provided.

What is claimed is: 
     
         1 . A method comprising:
 interrogating a biological sample from a subject for at least one indicium of a variant JCV VP1 capsid protein that comprises a substitution of amino acid residue 122, and   wherein the subject is determined to have an increased susceptibility for PML if the sample comprises the at least one indicium.   
     
     
         2 . The method of  claim 1 , further comprising interrogating the biological sample for at least one indicium of a variant JCV VP1 capsid protein that comprises a substitution of at least one of amino acid residues 2, and 66. 
     
     
         3 . The method of  claim 2 , wherein the sample is interrogated using an assay capable of detecting at least one indicium of each of variant JCV VP1 capsid proteins having a substitution of at least one of amino acid residues 2, 66, and 122, and wherein the subject is determined to have an increased susceptibility for PML if the sample comprises at least one indicium of at least one of the variant JCV VP1 capsid proteins. 
     
     
         4 . The method of  claim 1 , further comprising interrogating the biological sample for at least one indicium of a variant JCV VP1 capsid protein that comprises a deletion of one or more of amino acid fragments 50-51, 54-55 and 123-125. 
     
     
         5 . The method of  claim 4 , wherein the sample is interrogated using an assay capable of detecting at least one indicium of each of variant JCV VP1 capsid proteins having a deletion of at least one of amino acid fragments 50-51, 54-55 and 123-125, and wherein the subject is determined to have an increased susceptibility for PML if the sample comprises at least one indicium of at least one of the variant JCV VP1 capsid proteins. 
     
     
         6 . The method of  claim 1 , further comprising interrogating the biological sample for at least one indicium of a variant JCV VP1 capsid protein suspected of having low sialic acid binding. 
     
     
         7 . The method of  claim 1 , further comprising interrogating the biological sample for at least one indicium of a variant JCV VP1 capsid protein that comprises a substitution of at least one of amino acid residues 55, 60, 265, 267, and 269. 
     
     
         8 . The method of  claim 7 , wherein the sample is interrogated using an assay capable of detecting at least one indicium of each of variant JCV VP1 capsid proteins having a substitution of at least one of amino acid residues 55, 60, 265, 267, and 269, and wherein the subject is determined to have an increased susceptibility for PML if the sample comprises at least one indicium of at least one of the variant JCV VP1 capsid proteins. 
     
     
         9 . The method of  claim 1 , wherein the biological sample is a blood sample. 
     
     
         10 . The method of  claim 1 , wherein the biological sample is a CSF sample. 
     
     
         11 . The method of  claim 1 , wherein the biological sample is a urine sample. 
     
     
         12 . The method of  claim 1 , wherein the subject is known to have been previously infected with a wild-type JCV. 
     
     
         13 . The method of  claim 12 , wherein a new biological sample from the subject is interrogated for at least one indicium of at least one variant JCV VP1 capsid protein at least twice each year. 
     
     
         14 . The method of  claim 1 , wherein the detection of at least one indicium of a variant JCV VP1 capsid protein is used to identify the subject as inappropriate for an immunosuppressive treatment. 
     
     
         15 . The method of  claim 1 , wherein the detection of at least one indicium of a variant JCV VP1 capsid protein is used to recommend a modification of an immunosuppressive treatment for the subject. 
     
     
         16 . The method of  claim 1 , wherein the absence of indicia of a variant JCV VP1 capsid protein is used to identify the subject as appropriate for an immunosuppressive treatment. 
     
     
         17 . The method of  claim 1 , wherein the absence of indicia of a variant JCV VP1 capsid protein is used to identify the subject as appropriate for continued immunosuppressive treatment. 
     
     
         18 . The method of  claim 1 , wherein the biological sample is interrogated for the presence of an antibody that is specific for a variant JCV VP1 capsid protein. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein the biological sample is interrogated for the presence of a variant JCV VP1 capsid protein. 
     
     
         21 . The method of  claim 1 , wherein the biological sample is interrogated for the presence of a nucleic acid sequence that encodes a variant JCV VP1 capsid protein. 
     
     
         22 . The method of  claim 20 , wherein the biological sample is interrogated using an ELISA based analysis.