1746. Novel BK Virus Variants in Pediatric Immunocompromised Patients
Session: Poster Abstract Session: Viral Infections; Pathogenesis and Epidemiology
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • IDSA 2013 SFC.pdf (1010.5 kB)
  • Background:

    BK virus (BKV) is a prominent post-transplant infection for pediatric kidney transplant and hematopoietic stem cell transplant patients. We do not know what differentiates the patient that manifests BK nephropathy or hemorrhagic cystitis from the patient who does not.  Genetic rearrangements in the non-coding control region (NCCR) may be a marker of BK end-organ disease. Little is known about genetic changes in the rest of the genome, which encodes five proteins: agnoprotein, VP1-3, Large T and small t antigen.  The aim of this study is to identify specific BKV strains (genetic variants) from immunocompromised pediatric patients that would predict higher risk of BKV disease.

    Methods:

    To detect specific BKV strains, we sequenced the entire BK genome. Long range inverse PCR with four primer sets was used to amplify the full BK genome and next generation sequencing was performed using the Ion TorrentTM Personal Genome Machine.  Plasma and urine samples from fifteen patients, five kidney transplant (17 plasma), eight hematopoietic stem cell transplant (17 urine and 1 plasma) and two oncology patients (2 urine) were sequenced. BK virus load for the 15 patients ranged from 2140 – 60,000,000 copies/ml.

    Results: We detected multiple novel mutations (amino acid substitutions) in all protein coding regions except for small T antigen (Table).

    Protein

    Number of Novel Mutations

    Agnoprotein

    4

    VP1

    6 (loops: AB-3; BC-1; EF-1; GH-1)

    VP2

    5

    VP3

    1

    Large T antigen

    13 (domains: p300-4; pRB-2; DNA binding-2; ATPase activity-2; p53-3)

    Small t antigen

    0

    Nine patients had multiple specimens sequenced (2-6 per patient). Patients with sampling greater than 2 months apart had different mutations in each sample. Patients with sampling ≤ 2 months apart had the same mutations in each sample with two exceptions. These two patients had different mutations detected in subsequent samples and both manifested BK end-organ disease.

    Conclusion:

    Pediatric immunocompromised patients harbor a diversity of BKV strains (or genetic variants), demonstrated by detection of different amino acid changes in the protein coding regions of BKV. The diversity of BKV strains suggests the possibility that specific viral strains or specific mutations may be associated with worse clinical outcomes.

    Sharon F. Chen, MD, MS1, Beatrix Kapusinszky, Msc, PhD2, Malaya K. Sahoo, PhD2, Fiona Yamamoto, Msc2, Kalyan Mallempati, MSc2, Lynn Kjelson, MPH, MMS, PA-C1, Matthew W. Anderson, MD, PhD3, Amy Gallo, MD4, Paul Grimm, MD1, Waldo Concepcion, MD4 and Benjamin Pinksy, MD, PhD2, (1)Pediatrics, Stanford University School of Medicine, Palo Alto, CA, (2)Pathology, Stanford University School of Medicine, Palo Alto, CA, (3)Diagnostic Laboratories, Bloodcenter of Wisconsin, Milwaukee, WI, (4)Surgery, Stanford University School of Medicine, Palo Alto, CA

    Disclosures:

    S. F. Chen, None

    B. Kapusinszky, None

    M. K. Sahoo, None

    F. Yamamoto, None

    K. Mallempati, None

    L. Kjelson, None

    M. W. Anderson, None

    A. Gallo, None

    P. Grimm, None

    W. Concepcion, None

    B. Pinksy, None

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.