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.
Rotavirus infection is an important cause of acute gastroenteritis in children, but the interaction between rotavirus and host cells is not completely understood. We isolated a wildtype (wt) rotavirus strain, ZTR-68(P [8] G1), which is derived from an infant with diarrhea in southwest China in 2010. In this study, we investigated host cellular miRNA expression profiles changes in response to ZTR-68 in early stage of infection to investigate the role of miRNAs upon rotavirus infection. Differentially expressed miRNAs were identified by deep sequencing and qRT-PCR and the function of their targets predicted by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. A total of 36 candidate miRNAs were identified. Comparative analysis indicated that 29 miRNAs were significantly down-regulated and 7 were up-regulated after infection. The data were provided contrasting the types of microRNAs in two different permissive cell lines (HT29 and MA104). The target assays results showed that mml-miR-7 and mml-miR-125a are involved in anti-rotavirus and virus-host interaction in host cells. These results offer clues for identifying potential candidates in vector-based antiviral strategies. J. Med. Virol. 88:1497-1510, 2016. © 2016 Wiley Periodicals, Inc.
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