238C Poster - 02. Immunity and the microbiome
Saturday April 09, 1:30 PM - 3:30 PM

Zika Virus infection in Drosophila brain activates host immune responses in a sex-dependent manner


Authors:
Ghada Tafesh; Ananda Kalukin; Ioannis Eleftherianos

Affiliation: The George Washington University

Keywords:
c. innate immunity; a. neural degeneration

With World Health Organization (WHO) scientists recently confirming an outbreak of Zika virus (ZIKV) in India, the characterization and understanding of the molecular mechanisms underlying immune responses against ZIKV have, once again, become urgent. ZIKV, a member of the Flaviviridae family, is transmitted to humans primarily by the infected Aedes mosquito species, causing neurologic complications that range from sensory neuropathy and seizures to congenital Zika syndrome (microcephaly) in infants born to mothers infected during pregnancy. Previous research presents compelling evidence that establishes the fruit fly Drosophila melanogaster as a reliable model for studying arboviruses, as many of the signaling pathways identified are evolutionarily conserved amongst insect species. Particularly, the large conservation between Drosophila and mosquitoes has paved the way for our study to provide novel insights into ZIKV pathogenesis and host antiviral immune function using a brain tumor Drosophila model. By examining gene expression in adult Drosophila, we show that ZIKV can replicate efficiently in the brain and activate various immune responses. More specifically, our results confirm that RNA interference (RNAi) plays a key role in limiting ZIKV replication in the brain, thus forming a potent antiviral defense in Drosophila and presenting a potentially powerful tool to combat the host brain tumor. Behavioral analysis also shows that ZIKV causes severe locomotor impairment in infected flies, a common phenotype of neurodegenerative diseases such as Zika. Most importantly, our observations show significantly higher ZIKV rates and effects in female flies than males, indicating possible differences in the rates of infection and susceptibility to the development of disease. These findings make it imperative to continue uncovering the specifics of the complex host-virus interactions and provide additional insights that can potentially be harnessed for the control of different viral pathogens and define the full spectrum of antiviral immunity across various hosts.