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Published on: July 13, 2019
Characterization of the VP1 loop mutations widespread among JC polyomavirus isolates associated with progressive
Huai-Ying Zheng1, Hiroshi Ikegaya, Tomokazu Takasaka
1Department of Urology, Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Abstract:
Recently, we found that JC polyomavirus (JCPyV) associated with progressive multifocal leukoencephalopathy (PML) frequently undergoes amino acid substitutions (designated VP1 loop mutations) in the outer loops of the major capsid protein, VP1. To further characterize the mutations, we analyzed the VP1 region of the JCPyV genome in brain-tissue or cerebrospinal fluid samples from 20 PML patients. VP1 loop mutations occurred far more frequently than silent mutations. Polymorphic residues were essentially restricted to three positions (55, 60, and 66) within the BC loop, one (123) within the DE loop, and three (265, 267, and 269) within the HI loop. The mutations at most polymorphic residues showed a trend toward a change to specific amino acids. Finally, we presented evidence that the VP1 loop mutations were associated with the progression of PML. These findings should form the basis for elucidating the biological significance of the VP1 loop mutations.
Insights
JC polyomavirus (JCPyV) VP1 loop mutations are common in progressive multifocal leukoencephalopathy (PML) patients. These specific JCPyV mutations correlate with PML disease progression.
Area of Science:
- Virology
- Neuroscience
- Genetics
Background:
- JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML).
- VP1 loop mutations in the JCPyV major capsid protein (VP1) are frequently observed in PML.
- The biological significance of these VP1 loop mutations remains unclear.
Purpose of the Study:
- To characterize VP1 loop mutations in JCPyV from PML patients.
- To investigate the association between VP1 loop mutations and PML progression.
Main Methods:
- Analysis of the VP1 region of the JCPyV genome.
- Examination of brain tissue and cerebrospinal fluid samples from 20 PML patients.
- Identification and characterization of amino acid substitutions in VP1 loops.
Main Results:
- VP1 loop mutations were significantly more frequent than silent mutations in JCPyV from PML patients.
- Specific polymorphic residues were identified in the BC, DE, and HI loops of VP1.
- A trend towards specific amino acid changes was observed at polymorphic sites.
- VP1 loop mutations were associated with PML progression.
Conclusions:
- VP1 loop mutations are a common feature of JCPyV in PML.
- The identified mutation patterns provide insights into JCPyV evolution during PML.
- Further research is needed to elucidate the biological impact of these VP1 loop mutations on JCPyV pathogenesis and PML progression.
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