A system for the analysis of BKV non-coding control regions: application to clinical isolates from an HIV/AIDS patient.
The human polyomavirus BK virus (BKV) is an important opportunistic pathogen whose disease prevalence continues to increase with the growing immunocompromised population. To date, the major determinant of replication in cell culture has not been formally proven. BKV exists as archetype virus and rearranged variants, which are classified based on the DNA sequence of their non-coding control regions (NCCRs). The archetype BKV NCCR is divided into five blocks of sequence and rearranged variants contain deletions and duplications of these blocks. In this study, a genetic system was developed and used to identify the major determinant of replication ability in primary renal proximal tubule epithelial cells, the natural host cell of BKV. This system was also used to analyze NCCR variants isolated from an immunocompromised patient which contain assorted rearrangement patterns and functional differences. This study solidifies the NCCR as the major genetic determinant of BKV replication ability in vitro.
Broekema
Nicole M
NM
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-5620, USA. broekenm@umich.edu
Abend
Johanna R
JR
Bennett
Shauna M
SM
Butel
Janet S
JS
Vanchiere
John A
JA
Imperiale
Michael J
MJ
D017088:AIDS-Related Opportunistic Infections / Q000821:virology; D001739:BK Virus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis / Q000302:isolation & purification; D004847:Epithelial Cells / Q000821:virology; D014644:Genetic Variation; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D006801:Humans; D016867:Immunocompromised Host; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000821:virology; D027601:Polyomavirus Infections / Q000821:virology*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014412:Tumor Virus Infections / Q000821:virology*; D014556:Urine / Q000821:virology; D014773:Virology / Q000379:methods; D014779:Virus Replication
D004279:DNA, Viral