Clinical polyomavirus BK variants with agnogene deletion are non-functional but rescued by trans-complementation

Virology. 2010 Mar 1;398(1):12-20. doi: 10.1016/j.virol.2009.11.029. Epub 2009 Dec 14.

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.

MeSH terms

  • Animals
  • BK Virus / genetics*
  • Burkitt Lymphoma
  • DNA, Viral
  • Gene Deletion
  • Gene Expression Regulation, Viral / physiology
  • Humans
  • Promoter Regions, Genetic / genetics
  • Viral Regulatory and Accessory Proteins / genetics*
  • Viral Regulatory and Accessory Proteins / metabolism*
  • Virus Replication / genetics*

Substances

  • DNA, Viral
  • Viral Regulatory and Accessory Proteins
  • agnoprotein, polyomavirus