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DNA rearrangement in the control region for early transcription in a human polyomavirus JC host range mutant capable of growing in human embryonic kidney cells

A human polyomavirus JC virus (JCV) host range mutant (JC-HEK) can grow in human embryonic kidney cells, whereas the brain cell-tropic wild-type JCV strain (Mad-1) cannot; JC-HEK contains two complementing defective DNAs, JC-HEK-A and JC-HEK-B. We determined the nucleotide sequence of the putative transcriptional control region of JC-HEK-A DNA that can induce T-antigen synthesis in human embryonic kidney cells and compared it with the sequence of JCV Mad-1 DNA. The JC-HEK-A control region was found to have a complex DNA rearrangement, namely, a partial local duplication of a noncoding region generating two extra replication origins and translocation of segments from the large-T-antigen gene (415 base pairs) and the VP-1 gene (78 base pairs). In the rearranged segment, JC-HEK-A had seven sets of the sequence 5'TGGA(T)A(T)A(T)3', which is found in the simian virus 40 enhancer core, whereas JCV Mad-1 had only one set in its control region. JC-HEK-A also had a 5'TGGAAGTGTAA3' sequence resembling the adenovirus early region 1A enhancer core sequence 5'AGGAAGTGAA3'. Because the viral enhancer is host discriminatory and because another human polyomavirus, BK virus, that grows well in human embryonic kidney cells has these signals in its control region, it is likely that some of the newly acquired signals in JC-HEK play an important role in the altered host range of JCV.