Program Schedule

464
BK Virus Genetic Changes in Pediatric Kidney Transplant Patients with Prolonged BK Viral Load

Session: Poster Abstract Session: Transplant Infectious Diseases
Thursday, October 9, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Background: BK virus (BKV) is a prominent post-transplant infection for pediatric kidney transplant patients. We do not know what differentiates the patient that manifests BK nephropathy or prolonged BK viral load from the patient who does not.  Little is known about genetic changes in the entire genome, which encodes five proteins: agnoprotein, VP1-3, Large T and small t antigen.  The overall aim of this study is to identify specific BKV strains (genetic variants) from pediatric kidney transplant 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. Longitudinal plasma samples were sequenced from 6 pediatric kidney transplant patients. BK viral load ranged from 103 to 106 during the sampling period. 

Results:

In the table below, amino acid substitutions accounting for ≥ 95% of the populationare listed for each BK protein. For an individual patient, the same high frequency amino acid substitutions were consistently found in multiple longitudinal blood samples (average 3 samples/patient). Patients with prolonged and sustained high BK viral load by PCR with or without BK nephropathy were more often associated with amino acid substitutions in the Large T antigen compared to the other proteins. Few significant genetic changes were identified overall.  

Patient

LT

VP1

VP2

Outcome

BK+ Duration

1

Q668E

L5F

S77R

-

BKN

BK VL 104

14m

2

-

 

-

BKN

BK VL 103

9m

3

S405C

S1421C

D241E

-

-

Persistent BK viral load

9m, now resolved

4

T592A

 

-

Persistent BK viral load

3m, now resolved

5

 

 

T341A

Persistent BK viral load

BK VL < 103

6m

6

D241E

 

 

BKN

BK VL 103

84m

BKN – BK nephropathy; BK VL – BK viral load; m-months

Conclusion:  Using next generation sequencing, genetic changes resulting in amino acid subsititutions can be detected throughout the entire BK virus genome but appear to concentrate in the Large T antigen in pediatric kidney transplant patients who have persistent BK viral load with or without BK nephropathy. Large T antigen is known to be important in polyomavirus replication. Genetic changes in BK virus appear to remain stable, without any significant new genetic changes appearing over time.

Sharon F. Chen, MD, MS1, 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, Benjamin a. Pinsky, MD, PhD5, Beatrix Kapusinszky, Msc, PhD2 and Katie Concepcion2, (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, (5)Pathology, Stanford Hospital and Clinics, Palo Alto, CA

Disclosures:

S. F. Chen, 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. A. Pinsky, None

B. Kapusinszky, None

K. Concepcion, None

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