Methods for the detection of JC polyoma virus
View Patent ↗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.
1. A method comprising:
contacting a solid surface that comprises an immobilized variant John Cunningham polyomavirus (JCV) VP1 capsid protein that has arginine at a position corresponding to amino acid 122 of SEQ ID NO: 1, with a biological sample obtained from a subject; and
assaying for the presence or absence of a serum antibody that binds to the immobilized variant JCV VP1 capsid protein.
2. The method of claim 1 , wherein the biological sample is a blood sample.
3. The method of claim 1 , wherein the biological sample is a serum sample.
4. The method of claim 1 , wherein the biological sample is a cerebrospinal fluid (CSF) sample.
5. The method of claim 1 , wherein the subject is known to have been previously infected with a wild-type JCV.
6. The method of claim 5 , wherein the presence or absence of the serum antibody to said variant of JCV capsid protein for the subject is assayed at least twice each year.
7. The method of claim 1 , wherein the assaying step comprises performing an enzyme-linked immunosorbent assay (ELISA) to detect the presence or absence of the antibody.
8. The method of claim 1 , further comprising assaying the biological sample obtained from the subject for the presence or absence of the variant JCV VP1 capsid protein.
9. The method of claim 8 , where the biological sample is assayed for the presence or absence of a nucleic acid encoding the variant JCV VP1 capsid protein.
10. The method of claim 1 , wherein the subject has the variant JCV VP1 capsid protein.
11. A method comprising:
obtaining from a subject a biological sample, wherein the subject has a variant John Cunningham polyomavirus (JCV) VP1 capsid protein that has arginine at a position corresponding to amino acid 122 of SEQ ID NO: 1;
contacting a solid surface that comprises an immobilized variant JCV VP1 capsid protein that has arginine at a position corresponding to amino acid 122 of SEQ ID NO: 1, with the biological sample; and
assaying for the presence or absence of a serum antibody that binds to the immobilized variant JCV VP1 capsid protein.
12. The method of claim 11 , wherein the biological sample is a blood sample.
13. The method of claim 11 , wherein the biological sample is a serum sample.
14. The method of claim 11 , wherein the biological sample is a cerebrospinal fluid (CSF) sample.
15. The method of claim 11 , wherein the assaying step comprises performing an enzyme-linked immunosorbent assay (ELISA) to detect the presence or absence of the antibody.