Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy

Figure 4

A sequential order of DNA sequence alterations in progression of the JCV archetype NCCR to a neurovirulent type. In this model mutations precede deletions, and deletions precede tandem duplication. Deletions may occur due to slippage and/or homologous recombination, and duplication may result from various forms of recombination. The possibility of specialized forms of recombination, such as V(D)J-like recombination, occurring within this series cannot be ruled out. Both deletion and duplication may be triggered by dsb caused by replication fork pausing or stalling. No individual step, denoted by an arrow, need be an extremely rare event, but the end result, a neurovirulent JCV form, would be a rarity.