Disruption of Zika Virus xrRNA1-Dependent sfRNA1 Production Results in Tissue-Specific Attenuated Viral Replication
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Lines and Viruses
2.2. Plasmids and Generation of the X1 Mutant
2.3. Rescue and Propagation of ZIKV
2.4. Virus Quantification
2.5. Northern Blot
2.6. In Vitro Viral Growth Kinetics Comparison
2.7. Animal Studies
2.8. Characterization of Infection in Adult Ifnar1−/− Mice
2.9. Infection in Pregnant Ifnar1−/− Mice
2.10. Tissue Viral Load by RT-qPCR
2.11. Infection of Adult HuSTAT2 Mice
2.12. ZIKV-Reactive IgG ELISA
2.13. FRNT Measurement of Serum Neutralization
2.14. Statistical Analysis
3. Results
3.1. Development of an Infectious ZIKV X1 Mutant
3.2. X1 Mutation Does Not Significantly Alter Viral Growth In Vitro
3.3. X1 ZIKV Is Attenuated in Adult Ifnar1−/− Mice and Produces Neutralizing Antibody Responses
3.4. X1 Is Attenuated in the Central Nervous System (CNS) Tissue of Adult Ifnar1−/− Mice
3.5. X1 ZIKV Replication Is Attenuated in the Placenta of Pregnant Ifnar1−/− Mice
3.6. Attenuated X1 ZIKV Generates a Strong Neutralizing Antibody Response in Transgenic STAT2 Mice
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sparks, H.; Monogue, B.; Akiyama, B.; Kieft, J.; Beckham, J.D. Disruption of Zika Virus xrRNA1-Dependent sfRNA1 Production Results in Tissue-Specific Attenuated Viral Replication. Viruses 2020, 12, 1177. https://doi.org/10.3390/v12101177
Sparks H, Monogue B, Akiyama B, Kieft J, Beckham JD. Disruption of Zika Virus xrRNA1-Dependent sfRNA1 Production Results in Tissue-Specific Attenuated Viral Replication. Viruses. 2020; 12(10):1177. https://doi.org/10.3390/v12101177
Chicago/Turabian StyleSparks, Hadrian, Brendan Monogue, Benjamin Akiyama, Jeffrey Kieft, and J. David Beckham. 2020. "Disruption of Zika Virus xrRNA1-Dependent sfRNA1 Production Results in Tissue-Specific Attenuated Viral Replication" Viruses 12, no. 10: 1177. https://doi.org/10.3390/v12101177