The lytic phase of JC virus (JCV) appears to be highly complex and remains elusive. A growing body of experimental evidence suggests that the regulation of JCV gene expression and replication requires, in addition to the presence of speci�c transcription factors, cooperativity between viral and cellular regulatory proteins. This cooperativity may be accomplished by physical interaction of the participant proteins on and/or off the viral DNA sequence. Here, we present evidence of speci�c physical and functional interaction between a cellular factor, YB-1, and the JCV early protein, T-antigen, and showed that both proteins play important roles in JCV gene transcription. Additionally, our data indicate that YB-1 also functionally interact with another viral protein, designated agnoprotein, which is expressed late during the course of infection, adding further complexity to the currently known picture on JCV gene regulation
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