Roles of LncRNAs in Viral Infections

Liu, Weiwei; Ding, Chan

Theiler's picornavirus is a natural pathogen of mice. A mouse lncRNA, NeST (Nettoie Salmonella pas Theiler's, cleanup Salmonella not Therler's), was identified in Tmevp3 locus on mouse chromosome10 through gene mapping, which is next to the IFN-γ coding gene Ifng (Gomez et al., 2013) . The transgenic mouse of T cell specific expression of NeST showed that Theiler's virus increased persistence but decreased Salmonella enterica pathogenesis. These observations were likely due to induction of IFN-γ transcription specifically in activated CD8+ T cells by NeST. NeST regulates epigenetic marking of the Ifng locus through interaction with a protein partner WDR5, a component of the H3K4 methyltransferase complex. Whether and how disease-associated SNPs alter human NeST expression and/or function has not been elucidated and should be addressed in future studies. Nucleus Serves as a structural scaffold for the formation of nuclear paraspeckles; enhances HIV production; facilitates the expression of antiviral genes including cytokines such as IL-8 by cooperative action of NEAT1 and SFPQ Guru et al., 1997; Saha et al., 2006; Bond and Fox, 2009; Clemson et al., 2009; Sasaki et al., 2009; Sunwoo et al., 2009; Zhang et al., 2013; Imamura et Regulates gene expression through epigenetic mechanisms; interacts with several virus-and host cell-encoded factors; and promotes LANA-episome disassociation through an interaction with LANA Sun et al., 1996; Ballestas et al., 1999; Borah et al., 2011; Rossetto and Pari, 2011 Rossetto et al., 2013 Rossetto et al., , 2016 Campbell et al., 2014; Uppal et LncRNA NRON (non-coding repressor of NFAT) was initially identified as an inhibitor of transcription factor NFAT (Willingham et al., 2005) . NRON interacts with KPNB1, CSE1L, and IQGAP1, which bind phosphorylated NFAT in cytoplasm and represses NFAT nuclear trafficking. When T cells are activated, dephosphorylated NFAT is released from the complex and enters the nucleus (Sharma et al., 2011) . This result suggests that lncRNA exists as a scaffold for a latent transcription factor. A recent study suggested that downregulation of NRON by HIV infection enhanced NFAT nuclear translocation and activity (Imam et al., 2015) . HIV also utilizes NRON to control the balance between viral reproduction and cell death through the HIV early expressed protein Nef and the late expressed protein Vpu to decrease and increase NRON expression at different infection stages respectively (Imam et al., 2015) .