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

PloS One
Brigitte BollagRichard J Frisque

Abstract

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. These latter sequences are the least conserved among the early coding regions of primate polyomaviruses. We investigated the ability of wild type and mutant forms of JCV tAg to interact with cellular proteins involved in regulating cell proliferation and survival. The JCV P99A tAg is mutated at a conserved proline, which in the SV40 tAg is required for efficient interaction with protein phosphatase 2A (PP2A), and the C157A mutant tAg is altered at one of two newly recognized LxCxE motifs. Relative to wild type and C157A tAgs, P99A tAg interacts inefficiently with PP2A in vivo. Unlike SV40 tAg, JCV tAg binds to the Rb family of tumor suppressor proteins. Viral DNAs expressing mutant t proteins replicated less efficiently than did the intact JCV genome. A JCV construct in...Continue Reading

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Related Concepts

Antigens, Neoplasm, Viral
Human Herpesvirus 5 species
DNA Replication
DNA, Viral
JC Virus
Early Promoters, Genetic
Plasma Protein Binding Capacity
Virus Replication
Retinoblastoma Protein
Viral Genome

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