A Mouse Model of Zika Virus Pathogenesis

By Helen M. Lazear, Jennifer Govero, A. Smith, Derek J. Platt, Estefania Fernandez, Jonathan J. Miner, Michael S. Diamond. Cell Host and Microbe, 2016

877 citations recorded by the source corpus.

SUMMARY Due to the ongoing Zika virus (ZIKV) epidemic and unexpected clinical outcomes including Guillain-Barré syndrome and birth defects, there is an urgent need for animal model development. We evaluated infection and pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and transgenic mice lacking components of the innate antiviral response. Whereas 4 to 6 week-old wild-type, Irf3−/−, Irf5−/−, and Mavs−/−, mice showed no overt clinical illness, Irf3−/− Irf5−/− Irf7−/− TKO and Ifnar1−/− mice developed neurological disease and succumbed to ZIKV infection. Ifnar1−/− mice sustained high viral loads in the brain and spinal cord, consistent with evidence that ZIKV causes neurodevelopmental defects in human fetuses. The highest viral loads were detected in the testes of Ifnar1−/− mice, which is relevant to sexual transmission of ZIKV. This model of ZIKV pathogenesis will be valuable for evaluating vaccines and therapeutics, as well as understanding basic mechanisms of disease pathogenesis and immune evasion.

Subfields: Infectious Diseases, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/561fe87e597eefa8d73e92d7bfc73fc1e86562c9

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In Infectious Diseases

Citations in the corpus

Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3 (2016, neutral): “Mouse neurospheres were utilized because of the large sample size and previous data suggesting robust reservoirs of ZIKV viral infection and ZIKV production in mouse brain tissues and their ability to recapitulate neurodegenerative phenotypes in vivo (Lazear et al., 2016; Rossi et al., 2016).”
Modified mRNA vaccines protect against Zika virus infection (2017, positive): “, 2016), some of these studies used immunocompetent strains for challenge, which do not support as efficient ZIKV infection due to a species-specific lack of antagonism of IFN signaling (Grant et al., 2016; Kumar et al., 2016; Lazear et al., 2016).”
Brain Region-specific Organoids using Mini-bioreactors for Modeling ZIKV Exposure (2016, neutral): “Two recent studies have shown few differences between properties of different ZIKV strains in different models (Bayer et al., 2016; Lazear et al., 2016).”
Zika virus targets human STAT2 to inhibit type I interferon signaling (2016, background): “In the last decades, mosquito-borne ﬂaviviruses have caused signiﬁcant epidemic outbreaks, including DENV, WNV, and, more recently, Zika virus (ZIKV), associated with dramatic expansion of their geographical distribution (Coffey et al., 2013; Lazear and Diamond, 2016).”