Type of Resources

Dissertation/Thesis

Date Created

12-12-2019

Abstract

Zika virus (ZIKV), a member of the genus Flavivirus, has become a major public health concern since 2007. During the most recent 2015 outbreak, ZIKV rapidly spread from South America to over 84 countries and territories across the world in two years. ZIKV has also been associated with previously uncharacterized neurological manifestations during the 2013 and 2015 outbreaks. The novel manifestations include Guillain-Barré Syndrome (GBS) in adults and Congenital Zika Syndrome (CZS) in newborns. GBS is a progressive paralysis caused by damage to the peripheral nervous system; while CZS is an all-encompassing term for the severe neurological and developmental complications observed in newborns infected with ZIKV in utero. The exceptional rate of spread and unique neurological involvement observed during recent outbreaks has established a significant demand to expand knowledge on ZIKV virulence and pathology in humans and other species that could serve as disease models. To date, only three mammalian species: the rhesus macaque (Macaca mulatta), guinea pig (Cavia porcellus), and laboratory mouse (Mus musculus) have been employed to study ZIKV pathology. Of the three aforementioned species, the most commonly utilized model for ZIKV research is a genetically-modified Type I Interferon (IFN) deficient laboratory mouse. Use of this model provides utility by recapitulating human-like disease; however, the host immune response of an immunodeficient animal does not accurately reflect an immunocompetent human immune response. The drawbacks created by the use of immunodeficient animal necessitate the development of a model where disease and the host immune response mirror human infections. Therefore, the current study looks to supplement the lack of ZIKV research across diverse species and provide the pilot data for justifying further research of the selected species as an immunocompetent animal model. This project examined ZIKV susceptibility and the host cell response of three primary cell cultures derived from less-conventional, yet immunocompetent, models of disease resistance or pathology; the deer mouse (Peromyscus maniculatus), Jamaican fruit bats (Artibeus jamaicensis) and Syrian golden hamster (Mesocricetus auratus). In the current study, we show that primary cell cultures derived from all three animal models are susceptibility to ZIKV infection. Between the three selected animal models, primary cell cultures from Jamaican fruit bats and Syrian golden hamsters demonstrated the highest permissibility to ZIKV replication and viral shedding. We also provide insight into the host cell Type I IFN immune response by elucidating the differential regulation of JAK1, STAT1, Oas1b and ISG15 steady state mRNA levels in response to ZIKV infection. As a whole, our findings supplement the lack of information of ZIKV research across a diversity of species and provides the pilot data required to warrant further investigation into all three species as immunocompetent ZIKV animal models.

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