Ross River Virus Provokes Differentially Expressed MicroRNA and RNA Interference Responses in Aedes aegypti Mosquitoes.

Alphaviruses are globally distributed and predominately transmitted by mosquitoes. Aedes species are common vectors for the clinically important alphaviruses-Chikungunya, Sindbis, and Ross River (RRV) viruses-with Aedes aegypti also being a vector for the flaviviruses dengue, Yellow Fever, and Zika viruses. Ae. aegypti was putatively implicated in the large 1979-1980 South Pacific Islands outbreak of RRV-the leading cause of arboviral disease in Australia today. The RNA interference (RNAi) defense response in mosquitoes involves a number of small RNAs, with their kinetics induced by alphaviruses being poorly understood, particularly at the tissue level. We compared the small RNA profiles between RRV-infected and noninfected Ae. aegypti midgut and fat body tissues at 2, 6, and 12 days post-inoculation (dpi). RRV induced an incremental RNAi response, yielding short interfering and P-element-induced-wimpy-testis (PIWI)-interacting RNAs. Fourteen host microRNAs were differentially expressed due to RRV with the majority in the fat body at 2 dpi. The largely congruent pattern of microRNA regulation with previous reports for alphaviruses and divergence from those for flaviviruses suggests a degree of conservation, whereas patterns of microRNA expression unique to this study provide novel insights into the tissuespecific hostvirus attributes of Ae. aegypti responses to this previously unexplored oldworld alphavirus.