Mutations in JC Virus Protein Linked to Brain Disease
Author Information
Author(s): Sunyaev Shamil R., Lugovskoy Alexey, Simon Kenneth, Gorelik Leonid
Primary Institution: Brigham and Women's Hospital, Harvard Medical School, Biogen IDEC
Hypothesis
Specific mutations in the viral VP1 protein are critical for the evolution of JC virus to the version associated with Progressive Multifocal Leukoencephalopathy (PML).
Conclusion
The study suggests that mutations in the JC virus VP1 protein enhance its ability to bind to receptors in the brain, potentially leading to PML.
Supporting Evidence
- Mutations in the VP1 protein were found more frequently in PML patients than in healthy individuals.
- Specific amino acid changes in VP1 were associated with enhanced binding to sialic acid, a receptor for JC virus.
- Statistical analysis indicated that certain codons in the VP1 protein evolved under positive selection in PML patients.
Takeaway
The JC virus can cause a serious brain disease in some people, and this study found that certain changes in the virus help it infect the brain better.
Methodology
The study analyzed JC virus VP1 sequences from 55 PML patients and 253 healthy individuals to identify mutations associated with PML.
Potential Biases
Potential conflicts of interest due to authors' affiliations with Biogen IDEC.
Limitations
The study's findings may be limited by the small sample size of PML sequences and the potential for undetected mutations.
Participant Demographics
The study included sequences from 55 PML patients and 253 healthy individuals.
Statistical Information
P-Value
2.5×10−7
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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