Viral lncRNA: A regulatory molecule for controlling virus life cycle

Wang, Ziqiang; Zhao, Yiwan; Zhang, Yaou

The intracellular antiviral immune response in host cells provides essential protection against virus infection. The innate immune response can be triggered by the interaction between host cell pathogen recognition receptors and viral surface proteins and the presence of viral products, such as nucleic acids, in the host cell. However, some lncRNA generated by viruses have shown their roles in imparting resistance to the antiviral immune responses ( Table 1) . As the predominant antiviral response against invading viruses, RNA interference (RNAi) is an intracellular process that is induced by double-stranded RNA (dsRNA) that results in the cleavage of both cellular and viral mRNAs into small interfering dsRNA (siRNA) [47] . In the presence of dsRNA, protein kinase RNAactivated (PKR) is autophosphorylated; in turn, PKR phosphorylates its substrate (eukaryotic initiation factor 2a), leading to translation cessation [48] . Recently, some virally encoded lncRNAs have been shown to be involved in the RNAi pathway via the modulation of PKR activity for viral survival. EBERs contribute to the maintenance of malignant phenotypes by binding PKR and abrogating its activity [49] . Additionally, the adenovirus-associated RNAs VAI RNA and VAII RNA can attenuate the RNAi pathway by directly inhibiting PKR activation [50, 51] and functioning as competitive substrates to squelch Dicer and interfere with its activity [52] . Another RNA encoded by the West Nile and dengue viruses (sfRNA) not only efficiently suppressed siRNA-and miRNA-induced RNAi pathways in both mammalian and insect cells partially by disturbing dsRNA cleavage [53] but also interfered with the RNAi pathway by inhibiting the RNase Dicer [54] .