Roles of LncRNAs in Viral Infections

Liu, Weiwei; Ding, Chan

The subgenomic flavivirus RNA (sfRNA) is 300-500 nt in length and is derived from the 3 ′ UTR of the RNA genome of flaviviruses, a large group of single-stranded, positive-sense RNA viruses including several human pathogenic viruses, such as yellow fever virus, JEV, dengue viruses, and West Nile virus (Calisher and Gould, 2003; Knipe and Howley, 2007) . SfRNA is a product of an incomplete degradation of genomic RNA by the host 5 ′ -3 ′ exoribonuclease XRN1 and sfRNA is involved in viral infection and host cell response modulation (Roby et al., 2014; Clarke et al., 2015; Bavia et al., 2016; Charley and Wilusz, 2016) . The rigid secondary structure stem-loop II located at the beginning of the 3 ′ UTR of the viral genome is resistant to nuclease XRN1 degradation and results in the production of sfRNA (Funk et al., 2010) . The sfRNA structure, a ringlike conformation, with the 5 ′ end of the resistant structure passing through the ring from one side of the fold to the other, is required for the formation sfRNA during flaviviral infection (Chapman et al., 2014) . SfRNA generated by the Dengue virus II infection can bind the host proteins G3BP1, G3BP2, and CAPRIN1 and inhibit ISG mRNA translation (Bidet et al., 2014) . SfRNA prevents tripartite motif 25 (TRIM25) deubiquitylation, which is critical for sustained and amplified RIG-I-induced type I IFN expression (Manokaran et al., 2015) . Production of sfRNA increases the replication efficiency of WNVs and is essential for virus-induced cytotoxicity in cell culture and for viral pathogenicity in mice (Pijlman et al., 2008) . However, the mechanisms underlying how sfRNA leads to increased virus replication and cell death remain unknown. SfRNA was also identified in JEV infection and in an RNA pseudoknot that is also necessary for production of yellow fever sfRNA (Lin et al., 2004; Silva et al., 2010) .