Discovery of frog virus 3 microRNAs and their roles in evasion of host antiviral responses

Frog virus 3 (FV3, genus Ranavirus) causes devastating disease in amphibian populations and is capable of subverting host immune responses. Evidence suggests that virus-encoded microRNAs (v-miRNAs) are implicated in host immunoevasion tactics. Thus, we sought to discover FV3-encoded v-miRNAs and to uncover their putative roles in immunoevasion. Small RNA libraries were generated from FV3-infected Xela DS2, a Xenopus laevis dorsal skin epithelial-like cell line, at 24- and 72-hours post-infection (hpi). We discovered 43 FV3 v-miRNAs and identified that 15 are upregulated at 24 hpi, while 18 are upregulated at 72 hpi. Target prediction analyses revealed that FV3 v-miRNAs target host genes involved in key antiviral signaling pathways, while gene ontology analyses suggest that FV3 v-miRNAs may broadly impact host cell function. This is the first study to experimentally detect mature v-miRNAs produced by FV3. Our findings highlight the possibility that ranaviral v-miRNAs facilitate immunoevasion of frog antiviral responses.