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Article

The Antiviral Small-Interfering RNA Pathway Induces Zika Virus Resistance in Transgenic Aedes aegypti

1
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA
2
Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2020, 12(11), 1231; https://doi.org/10.3390/v12111231
Received: 8 October 2020 / Revised: 27 October 2020 / Accepted: 28 October 2020 / Published: 30 October 2020
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
The resurgence of arbovirus outbreaks across the globe, including the recent Zika virus (ZIKV) epidemic in 2015–2016, emphasizes the need for innovative vector control methods. In this study, we investigated ZIKV susceptibility to transgenic Aedes aegypti engineered to target the virus by means of the antiviral small-interfering RNA (siRNA) pathway. The robustness of antiviral effector expression in transgenic mosquitoes is strongly influenced by the genomic insertion locus and transgene copy number; we therefore used CRISPR/Cas9 to re-target a previously characterized locus (Chr2:321382225) and engineered mosquitoes expressing an inverted repeat (IR) dsRNA against the NS3/4A region of the ZIKV genome. Small RNA analysis revealed that the IR effector triggered the mosquito’s siRNA antiviral pathway in bloodfed females. Nearly complete (90%) inhibition of ZIKV replication was found in vivo in both midguts and carcasses at 7 or 14 days post-infection (dpi). Furthermore, significantly fewer transgenic mosquitoes contained ZIKV in their salivary glands (p = 0.001), which led to a reduction in the number of ZIKV-containing saliva samples as measured by transmission assay. Our work shows that Ae. aegypti innate immunity can be co-opted to engineer mosquitoes resistant to ZIKV. View Full-Text
Keywords: Aedes aegypti; Zika virus; transgenesis; RNAi; siRNAs; antiviral immunity; arbovirus; CRISPR/Cas9 Aedes aegypti; Zika virus; transgenesis; RNAi; siRNAs; antiviral immunity; arbovirus; CRISPR/Cas9
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MDPI and ACS Style

Williams, A.E.; Sanchez-Vargas, I.; Reid, W.R.; Lin, J.; Franz, A.W.E.; Olson, K.E. The Antiviral Small-Interfering RNA Pathway Induces Zika Virus Resistance in Transgenic Aedes aegypti. Viruses 2020, 12, 1231. https://doi.org/10.3390/v12111231

AMA Style

Williams AE, Sanchez-Vargas I, Reid WR, Lin J, Franz AWE, Olson KE. The Antiviral Small-Interfering RNA Pathway Induces Zika Virus Resistance in Transgenic Aedes aegypti. Viruses. 2020; 12(11):1231. https://doi.org/10.3390/v12111231

Chicago/Turabian Style

Williams, Adeline E., Irma Sanchez-Vargas, William R. Reid, Jingyi Lin, Alexander W.E. Franz, and Ken E. Olson 2020. "The Antiviral Small-Interfering RNA Pathway Induces Zika Virus Resistance in Transgenic Aedes aegypti" Viruses 12, no. 11: 1231. https://doi.org/10.3390/v12111231

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