Heterogeneity in inhibition of genetically diverse dengue virus strains by Wolbachia
Sodeinde A, Finch E, Li K, Breban MI, Bourgikos E, Nolan BL, Feriancek NM, Ott IM, Bakker JW, Hill V, Ross PA, Gu X, Huang AT, Salje H, Grubaugh ND, Vogels CBF
Applications: IF
Reactive species: DENV
"Abstract: The release of Aedes aegypti mosquitoes transinfected with the virus-inhibiting Wolbachia bacterium has the potential to reduce the burden caused by dengue virus (DENV). However, the robustness of this control strategy across the wide genetic diversity of DENV remains unknown. Here, we systematically tested two commonly used Wolbachia strains (wAlbB and wMelM) for their ability to inhibit 60 genetically diverse DENV isolates spanning all four serotypes. We found stronger inhibition by wMelM (median relative dissemination: 0.04) than wAlbB (median relative dissemination: 0.19). Furthermore, while we found substantial heterogeneity in inhibition across DENV isolates, we found that more DENV-3 isolates were weakly inhibited (median relative dissemination: 0.47 for wAlbB and 0.39 for wMelM) compared to the other serotypes (median relative disseminations: 0.10-0.18 for wAlbB and 0-0.11 for wMelM). Using transmission dynamic models, we further showed that differential Wolbachia inhibition results in increased probability of reemergence, particularly in high transmission intensity settings, with strong selection for DENV strains that have higher relative dissemination in mosquitoes. Our work highlights the importance of considering DENV genetic diversity, including the long-term risk of selection, in Wolbachia-based control interventions."
Article snippet: Primary and secondary antibodies were diluted in blotto at 1:1000. Fixed plates were incubated with 200 µL antibodies for 1.5 hours, at 37ºC. Mouse anti-DENV type 1,2,3,4 monoclonal primary antibodies (Creative-Diagnostics, #DCABH-10243) were used for DENV-1, DENV-2, and DENV-3, but did not work for DENV-4 viruses. 
Figure 1. Selection of 60 dengue virus isolates representing all four serotypes (DENV-1 to DENV-4). 
Figure 2. Correlation plot comparing focus forming units to DENV genome equivalents.
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![The purity of Recombinant DENV type 4 NS2B-NS3 (Fragment) [His] >85%, determined by SDS-PAGE](https://resource.creative-diagnostics.com/diagnostics/productimages-1/DAGA-1069-1.jpg)
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