Overall, this proposal seeks to define the role of the virome (eukaryotic viruses and bacteriophages) and bacterial microbiome in the health and BK disease of kidney transplant recipients. BK polyomavirus-associated nephropathy (BKVAN) is a major cause of kidney transplant failure. While the mechanistic basis for BKVAN progression is poorly understood, BK viremia is the most consistent surrogate marker for BKVAN. Little else is known about how the virome and bacterial microbiome impacts health and disease in kidney transplantation. In particular, the previously uncharacterized human urinary virome is a significant gap in our understanding of the human microbiome. To address this, we will analyze the circulatory (plasma) virome in a unique longitudinal cohort of kidney transplant recipients and assess their correlates with immunosuppression and BK viremia. Additionally, by defining the urinary virome and bacterial microbiome, we will have an unprecedented opportunity to examine microbiome interactions in the urinary tract. This will allow us to define novel interactions between BK disease and the virome, and explore the mechanisms by which microbiome alterations contribute to the health and disease of kidney transplant recipients. These findings could lead to a better understanding of the early events leading up to BK disease and a novel approach to monitor functional immunocompetence levels through the individual?s virome and microbiome. The mentored K99 phase with Dr. David Wang (Mentor), Dr. Herbert ?Skip? Virgin (Co-mentor) and Dr. Daniel Brennan (Advisor) will support critical training and facilitate the transition to address these questions in a new research field of kidney transplantation.

Public Health Relevance

Approximately 16,000 kidney transplants are performed each year in the US. In this proposal, we will gain a better understanding of how changes in the resident viruses and bacteria of kidney transplant patients are affected in those who develop kidney disease and those that do not. This will lead to the advancement of precision medicine, where we will be able to personalize the prevention and treatment of diseases to individual transplant recipients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Career Transition Award (K99)
Project #
1K99DK107923-01A1
Application #
9179528
Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK-D)
Program Officer
Rankin, Tracy L
Project Start
2016-09-13
Project End
2017-09-12
Budget Start
2016-09-13
Budget End
2017-09-12
Support Year
1
Fiscal Year
2016
Total Cost
$91,500
Indirect Cost
$6,778
Name
Washington University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Zhao, Guoyan; Wu, Guang; Lim, Efrem S et al. (2017) VirusSeeker, a computational pipeline for virus discovery and virome composition analysis. Virology 503:21-30
Lim, Efrem S; Brennan, Daniel C (2017) A Snapshot of Antibody-Mediated Rejection Goes Viral. Transplantation 101:227
Janowski, Andrew B; Krishnamurthy, Siddharth R; Lim, Efrem S et al. (2017) Statoviruses, A novel taxon of RNA viruses present in the gastrointestinal tracts of diverse mammals. Virology 504:36-44