Human neurotropic polyomavirus, JC virus, late coding region encodes a novel nuclear protein, ORF4, which targets the promyelocytic leukemia nuclear bodies (PML-NBs) and modulates their reorganization

We previously reported the discovery and characterization of two novel proteins (ORF1 and ORF2) generated by the alternative splicing of the JC virus (JCV) late coding region. Here, we report the discovery and partial characterization of three additional novel ORFs from the same coding region, ORF3, ORF4 and ORF5, which potentially encode 70, 173 and 265 amino acid long proteins respectively. While ORF3 protein exhibits a uniform distribution pattern throughout the cells, we were unable to detect ORF5 expression. Surprisingly, ORF4 protein was determined to be the only JCV protein specifically targeting the promyelocytic leukemia nuclear bodies (PML-NBs) and inducing their reorganization in nucleus. Although ORF4 protein has a modest effect on JCV replication, it is implicated to play major roles during the JCV life cycle, perhaps by regulating the antiviral response of PML-NBs against JCV infections and thus facilitating the progression of the JCV-induced disease in infected individuals.