title: Functional comparison of PML-type and archetype strains of JC virus.
abstract: Isolates of the human polyomavirus JC can be grouped as either PML-type or archetype strains primarily on the basis of divergence in their regulatory regions. Only PML-type viruses have so far been found to be associated with the human demyelinating disease progressive multifocal leukoencephalopathy. Here we have compared the functional properties of archetype and PML-type regulatory regions with regard to DNA replication and viral gene expression. No significant differences could be detected between archetype and PML-type regions in their ability to direct episomal DNA replication in the presence of JC virus T antigen. When viral gene expression was examined, early- and late-gene promoters from all PML-type strains exhibited a significantly higher activity in glial than in nonglial cells. Surprisingly, archetype strain promoters were also preferentially active in glial cells, although this effect was less pronounced than in PML-type strains. Furthermore, all promoters from archetype strains reacted to the presence of viral T antigen or the glial transcription factor Tst-1/Oct6 in a manner similar to the promoters of the PML-type viral strain Mad-1. Interestingly, T antigen and Tst-1/Oct6 were found to function in a species-specific and cell-type-specific manner, respectively. We concluded from our experiments that the differences in the regulatory regions cannot account for the different biology of archetype and PML-type viral strains.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universität Hamburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Sock
authors.forename: K
authors.initials: K
authors.lastname: Renner
authors.forename: D
authors.initials: D
authors.lastname: Feist
authors.forename: H
authors.initials: H
authors.lastname: Leger
authors.forename: M
authors.initials: M
authors.lastname: Wegner
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D004261:DNA Replication; D004279:DNA, Viral; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D014644:Genetic Variation; D006801:Humans; D007577:JC Virus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000821:virology*; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000166:cytology / Q000821:virology; D050816:Octamer Transcription Factor-6; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism; D014412:Tumor Virus Infections / Q000821:virology*; D014779:Virus Replication
chemical_list: D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C494178:POU3F1 protein, human; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6