Summary auto-generated
This study presents a comprehensive phylogenetic analysis of 22 complete JC virus (JCV) genomes to clarify evolutionary relationships among JCV types. JCV is a human polyomavirus that establishes persistent kidney infections and causes progressive multifocal leukoencephalopathy (PML), a demyelinating brain disease in immunocompromised individuals. Previous studies identified four main JCV types with geographic associations: Type 1 (European), Type 2 (Asian), Type 3 (African), and Type 4 (putative recombinant found in the United States). The researchers analyzed 4,854 base pairs from complete genomes (excluding the variable regulatory region) using three phylogenetic methods: neighbor-joining, UPGMA, and maximum parsimony. The whole genome approach provided a fourfold increase in phylogenetically informative sites compared to earlier partial sequence analyses. Results showed that Type 1 strains diverged early in JCV evolution, and all major genotypes form well-supported distinct clades. Type 4's apparent recombinant nature was most clearly supported by parsimony analysis. This is the first complete genome phylogenetic study of JCV, substantially improving upon earlier analyses limited to the 610 base pair V-T intergenic region.
Key findings
- Whole genome analysis of 22 JCV genomes provides fourfold more phylogenetically informative sites (172 sites) compared to the V-T region alone (41 sites), substantially improving phylogenetic resolution
- All three phylogenetic methods consistently identified distinct clades for Types 1, 2A/2C, 2B, and 3, with high bootstrap support values (55-100%), confirming these represent true genotypes
- Type 1 strains appear to have diverged early in JCV evolution, suggesting early geographic separation, while Type 4 shows evidence of recombination between Types 1 and 3
- Maximum parsimony effectively discriminates Type 4 from Type 1 by detecting VP1 gene fragments derived from Type 3, suggesting parsimony may be superior for analyzing recombinant JCV strains
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Abstract
The polyomavirus JC (JCV) establishes a persistent infection in the kidneys, and is the virus agent that causes the demyelinating disease progressive multifocal leukoencephalopathy. PCR and DNA sequence analyses of partial JCV genomes have shown that there are at least four main JCV types, each associated with a specific geographical region. Type 1 is of European origin, Type 2 is Asian, Type 3 is found in individuals of African decent and Type 4 is a potential recombinant of Types 1 and 3, and is widely distributed throughout the population of the United States. A comprehensive phylogenetic analysis of 22 complete JCV genomes excluding part of the regulatory region was accomplished using neighbour-joining, UPGMA and maximum parsimony methods. The resulting UPGMA and parsimony phylogenies suggest that the European Type 1 strains diverged from the other types during the evolution of JCV and that each of the other genotypes (and subtypes) falls into well- supported clades. This is the first whole genome approach to phylogeny reconstruction for JCV and represents a significant improvement over earlier studies that were limited to partial JCV sequences and the neighbour-joining method.