title: Clinical polyomavirus BK variants with agnogene deletion are non-functional but rescued by trans-complementation.
abstract: High-level replication of polyomavirus BK (BKV) in kidney transplant recipients is associated with the emergence of BKV variants with rearranged (rr) non-coding control region (NCCR) increasing viral early gene expression and cytopathology. Cloning and sequencing revealed the presence of a BKV quasispecies which included non-functional variants when assayed in a recombinant virus assay. Here we report that the rr-NCCR of BKV variants RH-3 and RH-12, both bearing a NCCR deletion including the 5' end of the agnoprotein coding sequence, mediated early and late viral reporter gene expression in kidney cells. However, in a recombinant virus they failed to produce infectious progeny despite large T-antigen and VP1 expression and the formation of nuclear virus-like particles. Infectious progeny was generated when the agnogene was reconstructed in cis or agnoprotein provided in trans from a co-existing BKV rr-NCCR variant. We conclude that complementation can rescue non-functional BKV variants in vitro and possibly in vivo.
authors.affiliation: Department of Microbiology and Virology, Institute of Medical Biology, University of Tromsø, Tromsø, Norway.
authors.forename: Marit Renée
authors.initials: MR
authors.lastname: Myhre
authors.forename: Gunn-Hege
authors.initials: GH
authors.lastname: Olsen
authors.forename: Rainer
authors.initials: R
authors.lastname: Gosert
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
authors.forename: Christine Hanssen
authors.initials: CH
authors.lastname: Rinaldo
mesh_terms: D000818:Animals; D001739:BK Virus / Q000235:genetics*; D002051:Burkitt Lymphoma; D004279:DNA, Viral; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics* / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics*; D000086082:Viroporin Proteins
chemical_list: D004279:DNA, Viral; D054334:Viral Regulatory and Accessory Proteins; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins