JC virus small T antigen binds phosphatase PP2A and Rb family proteins and is required for efficient viral DNA replication activity.

Background: The human polyomavirus, JC virus (JCV) produces five tumor proteins encoded by transcripts alternatively spliced from one precursor messenger RNA. Significant attention has been given to replication and transforming activities of JCV's large tumor antigen (TAg) and three T' proteins, but little is known about small tumor antigen (tAg) functions. Amino-terminal sequences of tAg overlap with those of the other tumor proteins, but the carboxy half of tAg is unique.

JC virus T'135, T'136 and T'165 proteins interact with cellular p107 and p130 in vivo and influence viral transformation potential.

The JC virus (JCV) regulatory proteins, large T antigen, small t antigen, T'135, T'136, and T'165, are encoded by five transcripts alternatively spliced from the viral early precursor mRNA. T antigen and the T' proteins share N-terminal amino acid sequences that include the L x CxE and J domains, motifs in SV40 T antigen known to mediate binding to the retinoblastoma (Rb) proteins and Hsc70, respectively. In this study, G418-resistant cell lines were created that express wild-type or mutant JCV T antigen and T' proteins individually or in combination.

T' proteins influence JC virus biology.

The JC virus early mRNA is alternatively spliced to yield five transcripts that encode large T antigen, small t antigen, T'(135), T'(136), and T'(165). The splicing process is regulated differentially in transformed versus lytically infected cells and temporally during the course of a productive infection. The authors have identified a potential exonic splicing enhancer near the 3' end of the early viral mRNA that, when mutated, results in altered splice site usage.

Purified JC virus T and T' proteins differentially interact with the retinoblastoma family of tumor suppressor proteins.

The amino termini of polyomavirus T antigens contain LXCXE and J domains, which are necessary for binding and inactivating the retinoblastoma family of tumor suppressors. Both of these motifs are found in the JC virus (JCV) early proteins T'(135), T'(136), and T'(165), leading to the suggestion that these recently discovered proteins complement the cell-cycle-deregulating function of the JCV large T antigen (TAg). To investigate this hypothesis, the three JCV T' proteins were produced in a baculovirus expression system and purified by immunoaffinity chromatography.

Purified JC virus T antigen derived from insect cells preferentially interacts with binding site II of the viral core origin under replication conditions.

The human polyomavirus JC virus (JCV) establishes persistent, asymptomatic infections in most individuals, but in severely immunocompromised hosts it may cause the fatal demyelinating brain disease progressive multifocal leukoencephalopathy. In cell culture JCV multiplies inefficiently and exhibits a narrow host range. This restricted behavior occurs, in part, at the level of DNA replication, which is regulated by JCV's multifunctional large tumor protein (TAg).