Transcription enhancers as major determinants of SV40 polyomavirus growth efficiency and host cell tropism.
The non-coding control region (NCCR) of polyomaviruses includes the promoters for early and late genes, a transcription enhancer and the origin of DNA replication. Particularly virulent variants of the human pathogens BKPyV and JCPyV, as well as of simian virus 40 (SV40), occur in vitro and in vivo. These strains often harbour rearrangements in their NCCR, typically deletions of some DNA segment(s) and/or duplications of others. Using an SV40-based model system we provide evidence that duplications of enhancer elements, whether from SV40 itself or from the related BKPyV and JCPyV, increase early gene transcription and replicative capacity. SV40 harbouring subsegments of the strong cytomegalovirus (HCMV) enhancer replicated better than the common 'wild-type' SV40 in the human cell lines HEK293 and U2OS. In conclusion, replacing the SV40 enhancer with heterologous enhancers can profoundly influence SV40's infective capacity, underscoring the potential of small DNA viruses to overcome cell type and species barriers.
Institute of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
Katharina
K
Schmidt
Institute of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
Simon
S
Keiser
Institute of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
Viola
V
Günther
Institute of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
Oleg
O
Georgiev
Transplantation & Clinical Virology, Department of Biomedicine, Petersplatz 10, University of Basel, CH-4009 Basel, Switzerland.|Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland.
Hans H
HH
Hirsch
Institute of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
Walter
W
Schaffner
Institute of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
Tobias
T
Bethge
D000818:Animals; D001739:BK Virus / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007577:JC Virus / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D013539:Simian virus 40 / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics; D056189:Viral Tropism / Q000235:genetics* / Q000502:physiology
D004279:DNA, Viral