Rotavirus-encoded virus-like small RNA triggers autophagy by targeting IGF1R via the PI3K/Akt/mTOR pathway.

Rotaviruses are double-stranded RNA viruses that are a major cause of viral diarrhea in infants. Examining virus-host cell interaction is important for elucidating mechanisms of virus proliferation in host cells. Viruses can create an environment that promotes their survival and self-proliferation by encoding miRNAs or miRNA-like molecules that target various host cell. However, it remains unclear whether RNA viruses encode viral miRNAs, and their regulation mechanisms are largely unknown. We previously performed deep sequencing analysis to investigate rotavirus-encoded miRNAs, and identified the small RNA molecule Chr17_1755, which we named RV-vsRNA1755. In our present study, we determined that RV-vsRNA1755 is encoded by the rotavirus NSP4 gene and that it targets the host cell IGF1R, which is part of the PI3K/Akt pathway. We further explored the biological characteristics and functions of RV-vsRNA1755.Our results suggest that rotavirus adapts to manipulate PI3K/Akt signaling at early phases of infection. RV-vsRNA1755 targets IGF1R, blockading the PI3K/Akt pathway and triggering autophagy, but it ultimately inhibits autophagy maturation. A mechanism through which rotavirus encodes a virus-like small RNA (RV-vsRNA1755) that triggers autophagy by targeting the host cell IGF1R gene was revealed. These data provide a theoretical basis for therapeutic drug screening targeting RV-vsRNA1755.