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. Journal of NeuroVirology (2001) 7, 288-292.
Keywords: agnoprotein; interaction; T-antigen; YB-1Human polyoma virus, JC virus (JCV), is a small DNA virus with a double-stranded covalently linked circular genome. It is the causative agent of progressive multifocal leukoencephalopathy where oligodendrocytes, the myelin-producing cells of central nervous system, are selectively destroyed by this virus. JCV genome is composed of three functional regions including the viral early-, late-coding regions, and noncoding regulatory region (Frisque et al, 1984). The viral early-and late-coding regions encode regulatory (large and small t-antigens) and structural (VP-1, -2, and -3) proteins, respectively. The viral late genome also contains an open-reading frame for a small auxiliary protein called agnoprotein, whose function in the viral life cycle is virtually unknown. The viral noncoding regulatory region contains the origin of DNA replication, promoter elements for both early and late genes, and cis-acting enhancer elements, which are characterized by two 98-bp tandem repeats.Transcriptional regulation of the JCV early and late promoters in the lytic cycle appears to be rather