Zika virus (ZIKV) is single stranded RNA virus of the Flaviviridae family. Closely related to other more well- known members of the flavivrus family including Yellow Fever virus, West Nile virus (WNV), Japanese Encephalitis virus, and Dengue virus (DENV), ZIKV is transmitted through the bite of an infected mosquito. Currently the Americas are experiencing an outbreak from this emerging virus that the World Health Organization has declared a Public Emergency of International Concern due to the newly found association of ZIKV infection with severe fetal anomalies including neural tube defects and intrauterine growth restriction. Previously ZIKV was only associated with mild disease in Africa and Asia where it has been endemic since its discovery in Uganda in 1947 and the current increase in morbidity associated with ZIKV infection is not well understood. Concurrent and waning DENV outbreaks, in French Polynesia and Brazil and respectively, have been hypothesized as a contributing factor due to the accepted paradigm of antibody-dependent enhancement of disease (ADE) in severe DENV infection, but evidence of ADE occurring in ZIKV disease has not been proven. Elucidation of the mechanisms responsible for the increased virulence of ZIKV as well as the development of vaccines and therapeutics are paramount. However, currently there are no established translational models in which to study ZIKV pathobiology. The olive baboon, Papio anubis, has been advanced as a translational model of infectious disease for multiple pathogens such as Bordetella pertussis and Respiratory Syncytial virus as well as other flaviviruses including WNV and DENV. We propose to conduct studies for the purpose of establishing the baboon as a translational model of ZIKV disease, and hypothesize that previous infection with DENV will impact the pathogenicity and immune response to ZIKV within the model. Together the proposed studies will establish a translational model of ZIKV disease and begin to clarify the mechanism of increased morbidity.

Public Health Relevance

The World Health Organization has declared the 2016 Zika virus epidemic in the Americas as a Public Health Emergency of International Concern. Previously unknown to the general public, Zika virus was formerly only associated with mild disease in Africa and Asia. However, with the 2013 outbreak in French Polynesia and the 2016 epidemic in the Americas, Zika virus has been associated with substantial birth defects including microcephaly and death as well as neurological disease in adults. As such, it is vital that novel vaccines to prevent disease and therapeutics to treat disease are developed. These studies will cultivate necessary tools for the evaluation of candidate vaccines and therapeutics.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZAI1)
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Challberg, Mark D
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University of Oklahoma Health Sciences Center
Schools of Medicine
Oklahoma City
United States
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Gurung, Sunam; Preno, Alisha N; Dubaut, Jamie P et al. (2018) Translational Model of Zika Virus Disease in Baboons. J Virol :