Large-scale viral surveillance studies are critical to monitoring the global emergence of infectious disease and yield important information about the prevalence and seasonality of circulating virus species and the possible existence of novel species. Many large epidemiologic studies that have been conducted in temperate countries have not been repeated in tropical settings, however, and are likely to reveal viral burden and incidence variations due to inherent environmental and social differences. Dengue virus (DV) is an archetypal emerging infectious disease that infects an estimated 50-100 million people annually in a rapidly expanding geographic range and is the most common vector-borne viral disease of humans. Currently available lab diagnostic methods, however, fail to detect DV infection in 30-70% of patients presenting with hallmark dengue symptoms. The purpose of this study is twofold: to use the best available diagnostic technologies to delineate the spectrum of viral pathogens in a developing tropical environment with respect to dengue-like illnesses and to utilize the data provided by the extensive screening as a platform for the discovery of novel or divergent human viral pathogens. In collaboration with Eva Harris, this study will use the Virochip (UCSF) to characterize human sera and PBMC samples from Nicaraguan patients from the proposed hospital-based study presenting with dengue-like symptoms over multiple seasons. This will allow us to capture both the prevalence, seasonality and dual infection rates for all known viruses in suspected dengue cases over time. We also propose to utilize ultra-deep sequencing for a select number of samples based on several criteria including severity of symptoms for discovery of previously uncharacterized agents. We will pursue full genome cloning and molecular characterization for promising leads, including development of PCR-based rapid diagnostics and serological reagents for subsequent association studies.

Public Health Relevance

Monitoring the threat of international emerging infectious disease requires proactive viral surveillance studies in tropical environments where many large epidemiologic studies have not been conducted. The convergence of viral diagnostic resources at UCSF and ongoing sample collection via the proposed hospital-based study in Nicaragua presents a rare opportunity to delineate the full spectrum of emerging and uncharacterized viral pathogens associated with pediatric dengue-like illness in a tropical setting using the most recently developed comprehensive molecular tools.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI065359-09
Application #
8462532
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
9
Fiscal Year
2013
Total Cost
$94,440
Indirect Cost
$9,644
Name
University of California Irvine
Department
Type
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Hertz, Tomer; Beatty, P Robert; MacMillen, Zachary et al. (2017) Antibody Epitopes Identified in Critical Regions of Dengue Virus Nonstructural 1 Protein in Mouse Vaccination and Natural Human Infections. J Immunol 198:4025-4035
Marques, Adriana R; Yang, Xiuli; Smith, Alexis A et al. (2017) Citrate Anticoagulant Improves the Sensitivity of Borreliella (Borrelia) burgdorferi Plasma Culture. J Clin Microbiol 55:3297-3299
Parameswaran, Poornima; Wang, Chunling; Trivedi, Surbhi Bharat et al. (2017) Intrahost Selection Pressures Drive Rapid Dengue Virus Microevolution in Acute Human Infections. Cell Host Microbe 22:400-410.e5
Bortell, Nikki; Flynn, Claudia; Conti, Bruno et al. (2017) Osteopontin Impacts West Nile virus Pathogenesis and Resistance by Regulating Inflammasome Components and Cell Death in the Central Nervous System at Early Time Points. Mediators Inflamm 2017:7582437
Barbour, Alan G (2017) Infection resistance and tolerance in Peromyscus spp., natural reservoirs of microbes that are virulent for humans. Semin Cell Dev Biol 61:115-122
Nualnoi, Teerapat; Norris, Michael H; Tuanyok, Apichai et al. (2017) Development of Immunoassays for Burkholderia pseudomallei Typical and Atypical Lipopolysaccharide Strain Typing. Am J Trop Med Hyg 96:358-367
Nakajima, Rie; Escudero, Raquel; Molina, Douglas M et al. (2016) Towards Development of Improved Serodiagnostics for Tularemia by Use of Francisella tularensis Proteome Microarrays. J Clin Microbiol 54:1755-65
Zeltina, Antra; Bowden, Thomas A; Lee, Benhur (2016) Emerging Paramyxoviruses: Receptor Tropism and Zoonotic Potential. PLoS Pathog 12:e1005390
Ziegler, Christopher M; Eisenhauer, Philip; Bruce, Emily A et al. (2016) A novel phosphoserine motif in the LCMV matrix protein Z regulates the release of infectious virus and defective interfering particles. J Gen Virol 97:2084-9
Park, Arnold; Yun, Tatyana; Hill, Terence E et al. (2016) Optimized P2A for reporter gene insertion into Nipah virus results in efficient ribosomal skipping and wild-type lethality. J Gen Virol 97:839-43

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