Bloodborne infectious agents, including novel / emerging pathogens of concern, pose a continual threat to our blood supply and the safety of the 5 million transfusions performed annually in the United States. Here we propose to apply two state-of-the-art diagnostic technologies, a pan-viral microarray called the Virochip and massively parallel deep sequencing, to comprehensively identify infectious agents in blood. The Virochip will be expanded to cover bloodborne nonviral as well as viral pathogens, and we will rigorously assess analytical test characteristics (e.g. sensitivity, specificity, limits of detection, accuracy) for detection of pathogens associated with the most common bloodborne infections, including malaria, Chagas disease, HIV, hepatitis B/C, and dengue virus. The expanded Virochip and deep sequencing will then be used to launch a broad- spectrum surveillance program for bloodborne infectious agents. We will initially focus on analyzing serum samples from patients with nonA-E clinical hepatitis and deferred blood donors with post-donation acute illness such as fever - samples which carry a high a priori probability of harboring known / novel infectious agents. We will analyze random individual or pooled serum samples from donors matched by age, sex, and geographic location for infectious agents circulating in our blood supply. We will perform whole-genome sequencing and epidemiological screening by serology and PCR for any novel viruses identified in transfused blood. A major goal of this research is to assess the utility of Virochip and deep sequencing as comprehensive pathogen screening tools for ensuring transfusion safety. Identification of novel infectious agents in blood will also spur further detailed investigations into their epidemiology and pathogenicity.

Public Health Relevance

Chiu, C. RELEVANCE Known as well as novel / emerging infectious agents continually threaten the safety of the 5 million transfusions performed annually in the United States, yet the lack of diagnostic tools able to comprehensively test for bloodborne pathogens or to identify novel / divergent strains has hindered surveillance efforts. This study proposes to investigate the utility of the Virochip, a pan-viral microarray, and massively parallel deep sequencing as complementary strategies for (1) broad-based detection of bloodborne pathogens, and (2) identification of novel / emerging infectious agents. The results from this study have the potential to advance these technologies for eventual FDA approval as broad-based screening tools to ensure transfusion safety, with significant clinical and public health implications. Identification of novel infectious agents in blood will also open up new avenues of research into their epidemiology and the threat that they pose to our blood supply. Page 1

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL105704-05
Application #
8828278
Study Section
Special Emphasis Panel (ZRG1-VH-E (50))
Program Officer
Mondoro, Traci
Project Start
2011-04-01
Project End
2016-03-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
5
Fiscal Year
2015
Total Cost
$573,600
Indirect Cost
$118,361
Name
University of California San Francisco
Department
Pathology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Seferovic, Maxim; Sánchez-San Martín, Claudia; Tardif, Suzette D et al. (2018) Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities. Sci Rep 8:6851
Langelier, Charles; Zinter, Matt S; Kalantar, Katrina et al. (2018) Metagenomic Sequencing Detects Respiratory Pathogens in Hematopoietic Cellular Transplant Patients. Am J Respir Crit Care Med 197:524-528
Gu, Wei; Miller, Steve; Chiu, Charles Y (2018) Clinical Metagenomic Next-Generation Sequencing for Pathogen Detection. Annu Rev Pathol :
Dudley, Dawn M; Van Rompay, Koen K; Coffey, Lark L et al. (2018) Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates. Nat Med 24:1104-1107
Thézé, Julien; Li, Tony; du Plessis, Louis et al. (2018) Genomic Epidemiology Reconstructs the Introduction and Spread of Zika Virus in Central America and Mexico. Cell Host Microbe 23:855-864.e7
Sánchez-San Martín, Claudia; Li, Tony; Bouquet, Jerome et al. (2018) Differentiation enhances Zika virus infection of neuronal brain cells. Sci Rep 8:14543
Faria, N R; Quick, J; Claro, I M et al. (2017) Establishment and cryptic transmission of Zika virus in Brazil and the Americas. Nature 546:406-410
Saito, Toshie; Miyagawa, Kazuya; Chen, Shih-Yu et al. (2017) Upregulation of Human Endogenous Retrovirus-K Is Linked to Immunity and Inflammation in Pulmonary Arterial Hypertension. Circulation 136:1920-1935
Castro-Wallace, Sarah L; Chiu, Charles Y; John, Kristen K et al. (2017) Nanopore DNA Sequencing and Genome Assembly on the International Space Station. Sci Rep 7:18022
Hixon, Alison M; Yu, Guixia; Leser, J Smith et al. (2017) A mouse model of paralytic myelitis caused by enterovirus D68. PLoS Pathog 13:e1006199

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