Extension of JC virus host range to monkey cells by insertion of a simian virus 40 enhancer into the JC virus regulatory region.
A chimeric polyomavirus genome was constructed by inserting the 72- and the 21-bp repeats of simian virus 40 (SV40) into the JC virus (JCV) regulatory region on the late side of the JCV 98-bp repeats. Although the chimeric polyomavirus DNA was able to replicate very well in human fetal glial cells, deletions were found in sequences of the regulatory region. DNA sequence analysis of a selected clone indicated a 294-bp deletion from the original construction that retained the sequences for the JCV replication origin, 78 bp of one 98-bp repeat, 33 bp of one SV40 72-bp repeat, and one intact 72-bp repeat. Of significant interest was that this genome demonstrated an extended species and cell-type host range, producing infectious virus in human fetal brain and embryonic kidney as well as in rhesus monkey fetal and adult glial cells. However, the species host range was not extended beyond primate cells since the chimeric polyomavirus was unable to multiply in rodent glial cells. Analysis of the viral RNA transcripts from either kidney or glial cells indicated that the major start sites for early RNA mapped within the JCV sequences of the regulatory region and major start sites for late RNA mapped within the JCV and SV40 sequences. This extension of the JC virus host range was most likely attributable to changes in the regulatory region and not the viral T protein since a recombinant DNA clone which placed the coding sequences for the wild-type JCV T protein subject to regulation by the deleted chimeric regulatory region showed a similar extension of host range.
Vacante
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Infectious Diseases Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland 20892.
Traub
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D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D002678:Chimera; D003588:Cytopathogenic Effect, Viral; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D006801:Humans; D007577:JC Virus / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D011120:Polyomavirus / Q000235:genetics*; D012367:RNA, Viral / Q000032:analysis; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D013539:Simian virus 40 / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D014779:Virus Replication
D004279:DNA, Viral; D012367:RNA, Viral