AUTHOR=Ford Suzanne A. , Albert Istvan , Allen Scott L. , Chenoweth Stephen F. , Jones Matthew , Koh Cassandra , Sebastian Aswathy , Sigle Leah T. , McGraw Elizabeth A. 

TITLE=Artificial Selection Finds New Hypotheses for the Mechanism of Wolbachia-Mediated Dengue Blocking in Mosquitoes

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01456

DOI=10.3389/fmicb.2020.01456

ISSN=1664-302X

ABSTRACT=<p><italic>Wolbachia</italic> is an intracellular bacterium that blocks virus replication in insects and has been introduced into the mosquito, <italic>Aedes aegypti</italic> for the biocontrol of arboviruses including dengue, Zika, and chikungunya. Despite ongoing research, the mechanism of <italic>Wolbachia-</italic>mediated virus blocking remains unclear. We recently used experimental evolution to reveal that <italic>Wolbachia-</italic>mediated dengue blocking could be selected upon in the <italic>A. aegypti</italic> host and showed evidence that strong levels of blocking could be maintained by natural selection. In this study, we investigate the genetic variation associated with blocking and use these analyses to generate testable hypotheses surrounding the mechanism of <italic>Wolbachia-</italic>mediated dengue blocking. From our results, we hypothesize that <italic>Wolbachia</italic> may block virus replication by increasing the regeneration rate of mosquito cells via the Notch signaling pathway. We also propose that <italic>Wolbachia</italic> modulates the host’s transcriptional pausing pathway either to prime the host’s anti-viral response or to directly inhibit viral replication.</p>