Temperature and sex shape Zika virus pathogenicity in the adult brain: A model for virus-associated neurological diseases.

Severe neurological complications affecting brain growth and function have been well documented in newborn and adult patients infected by Zika virus (ZIKV), but the underlying mechanisms remain unknown. Here we use a mutant, (), with a mutation in the () locus that exhibits both aberrant continued proliferation and progressive neurodegeneration in the adult brain. We report that temperature variability is a key driver of ZIKV pathogenesis, thereby altering host mortality and causing motor dysfunction in a sex-dependent manner. Furthermore, we show that ZIKV is largely localized to the brain and activates the RNAi and apoptotic immune responses. Our findings establish an model to study host innate immune responses and highlight the need of evaluating neurodegenerative deficits as a potential comorbidity in ZIKV-infected adults.