Identification of diagnostic and prognostic host biomarkers of Zika virus infection by transcriptome profiling There is currently an unprecedented ongoing outbreak of Zika virus (ZIKV) in the Americas, with more than 100,000 cases reported to date. Limitations to existing diagnostic tests include lack of specificity for antibody-based assays and a very narrow time window for PCR (<1 week). Better diagnostic tests are urgently needed to diagnose ZIKV infection. In addition, the weight of the combined evidence now shows that ZIKV is directly responsible for devastating adverse fetal outcomes in infected pregnant women, including in utero demise and microcephaly. There is currently no laboratory test to monitor infected women and assess their risk for fetal complications. Here we propose use transcriptome profiling analysis by RNA-Seq next-generation sequencing of blood, urine, and saliva samples from acutely infected patients to diagnose ZIKV infection, and of serially collected samples from ZIKV-infected pregnant women to monitoring the dynamics of the host response. The goal is to identify diagnostic and prognostic host biomarkers that may be correlated with active infection (for diagnosis) as well as fetal infection and outcomes in pregnant women, and that can be used to develop new assays for monitor ZIKV infection and disease.

Public Health Relevance

Identification of diagnostic and prognostic host biomarkers of Zika virus infection by transcriptome profiling There is currently an unprecedented emerging outbreak of Zika virus (ZIKV) in the Americas, a mosquito-borne virus that is associated with severe fetal complications such as microcephaly in pregnant women. Better diagnostic tests are urgently needed to diagnose and monitor ZIKV infection. Here we propose to identify biomarkers of ZIKV infection that can be used for diagnosis in infected patients and to monitor fetal infection and outcomes in pregnant women who are infected with ZIKV.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI129455-02
Application #
9402050
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Challberg, Mark D
Project Start
2016-12-14
Project End
2019-11-30
Budget Start
2017-12-01
Budget End
2019-11-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Pathology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
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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