# Genetic Diversity of the Polyomavirus JC and Implications for the Pathogenesis of Progressive Multifocal Leukoencephalopathy

## TL;DR

This review discusses the genetic diversity of JC Polyomavirus and how it relates to a rare brain disease called progressive multifocal leukoencephalopathy.

## Contribution

The paper provides a summary of archetype and prototype JCPyV strains to help interpret new sequencing data and distinguish natural polymorphism from prototype-specific mutations.

## Key findings

- JCPyV exists in two forms: archetype in the periphery and prototype in the central nervous system.
- The prototype form contains recombinations in the non-coding control region and mutations in the VP1 capsid protein.
- Natural polymorphism exists between JCPyV genotypes, which can be distinguished from prototype-specific mutations.

## Abstract

JC Polyomavirus (JCPyV) is a non-enveloped virus with circular double stranded DNA responsible for the rare but fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). In its host, this virus exists in two different forms: one found in the periphery, named archetype, and another found in the central nervous system, named prototype. This form usually harbors recombinations in the non-coding control region (NCCR), a key region that contains sequences regulating viral replication and containing binding sites for cellular transcription factors. This form also contains mutations in the capsid protein, especially VP1. Due to the diversity of the JCPyV, a natural polymorphism also exists between the different genotypes. In this review, we aimed to summarize the main features of the archetype and prototype strains in order to facilitate the interpretation of sequence data that are increasingly generated by new sequencing technologies. This will also help to distinguish mutations associated with the natural polymorphism from those specific to the prototype form.