Model for agnoprotein/LT-Ag interaction in the nucleus. Upon translation of the JCV late transcripts (1), agnoprotein mostly localizes to cytoplasm, largely accumulating around the perinuclear area (2) (Fig. 1B) and a small amount of the protein, however, translocates into the nucleus (3), where it interacts with LT-Ag off the DNA (Safak et al., 2001) and perhaps induces conformational changes on LT-Ag too (6). Subsequently, agnoprotein separates from the LT/Agno complex (4) and liberated LT-Ag then binds to Ori (Fig. 2A) more efficiently in a double hexamer manner (7), unwinds DNA and initiates viral DNA replication which may lead to an increased viral DNA replication (8).