This R24 application is to promote nonhuman primate (NHP) health and the quality of NHP research resources for translational work by using metagenomics to improve diagnosis of infectious diseases with an emphasis on gastrointestinal (GI) disorders. Despite significant advances in the diagnosis of infectious diseases, unrecognized or adventitious agents in NHPs have the potential to confound experimental work. At the Tulane National Primate Research Center (TNPRC) over the past 3 years, we averaged 467 cases of GI disease/year presenting as animals with diarrhea. The average cost alone for case management of these animals was over $530,000/year. We have developed technologies that can readily, in a single test, detect multiple novel viruses, other potential pathogens, and the structure of the microbiome in fecal samples and intestinal tissues. Leveraging the resources of the laboratory of co-PI Dr. Skip Virgin at Washington University School of Medicine and the resources of the TNPRC under co-PI Dr. Andrew Lackner provides a unique opportunity to expand existing NHP models to include microbiome studies and to bring new approaches to the diagnosis of infections in NHPs. NHPs are used extensively in biomedical research programs. The overall objective of this proposal is to integrate clinical and pathology data with advanced next- generation sequencing and computational methods to facilitate the early recognition and diagnosis of established and novel infectious diseases of NHPs in the context of the microbiome. With these data we will create a central annotated repository of sequence and pathology information that will foster rapid dissemination of information on pathogens, and potential pathogens, across the NHP research community. Our goal is to provide this resource to both commercial and academic concerns to optimize the value of NHPs in translational research (see letters of support for documentation of the need for such a program). To this end we propose to establish a Primate Infectious Disease Resource (PIDR) that takes advantage of unique resources and specialized expertise present at WUSM and the TNPRC through the following aims.
Specific aim 1 : To establish a Primate Infectious Disease Resource to support NHP national biomedical research objectives.
Specific aim 2 : To define enteric metagenomic profiles from National Primate Research Center (NPRC) specific pathogen free (SPF) NHP breeding colonies and correlate these profiles with differences in gastrointestinal pathology and disease.
Specific aim 3 : To define the importance of selected new viruses or other pathogens identified via metagenomics and develop standard diagnostic tools for agents of proven relevance to NHP health.

Public Health Relevance

Significant advances in sequencing technologies and bioinformatics now allow detection of organisms in the microbiome including bacteria, archaea, viruses, fungi, and the meifauna. These technologies have not yet been applied to enhance disease diagnosis and the health of precious nonhuman primates in the National Primate Research Center program. This application is to create a Primate Infectious Disease Resource, leveraging the complimentary expertise of the two PI's, to accomplish this goal.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Resource-Related Research Projects (R24)
Project #
5R24OD019793-04
Application #
9444409
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Contreras, Miguel A
Project Start
2015-04-01
Project End
2019-02-28
Budget Start
2018-03-01
Budget End
2019-02-28
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Washington University
Department
Pathology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Monaco, Cynthia L; Kwon, Douglas S (2017) Next-generation Sequencing of the DNA Virome from Fecal Samples. Bio Protoc 7:
Pfeiffer, Julie K; Virgin, Herbert W (2016) Viral immunity. Transkingdom control of viral infection and immunity in the mammalian intestine. Science 351:
Reese, Tiffany A; Bi, Kevin; Kambal, Amal et al. (2016) Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response. Cell Host Microbe 19:713-9
Monaco, Cynthia L; Gootenberg, David B; Zhao, Guoyan et al. (2016) Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome. Cell Host Microbe 19:311-22