Roles of LncRNAs in Viral Infections

Liu, Weiwei; Ding, Chan

Using Next Generation Sequencing (NGS), differential expression of approximately 500 annotated lncRNAs and 1,000 non-annotated genomic regions after SARS coronavirus infection were identified in mice (Peng et al., 2010) . This research represented the first discovery of the widespread differential expression of lncRNAs in response to virus infection and suggested that lncRNAs may be involved in regulating the antiviral host response. Recently, Qi Zhang et al found 646 lncRNAs were upregulated and 424 lncRNAs were downregulated in latent human cytomegalovirus (CMV) infection on THP-1 cells using RNA-seq analysis . However, the critical lncRNA in latent human CMV infection has not been identified and its role has not been elucidated yet. Moreover, additional lncRNAs associated with the virus infection in the host have been identified. Significant differential expression of lncRNAs is induced by virus and regulated by RNA virus or DNA virus infection. In turn, these lncRNAs regulate the host innate immune response including the pathogen recognition receptor (PRR)-related signaling, the production of IFNs and cytokines (Carpenter, 2016; Ouyang et al., 2016) . For example, in HCV infection, lncRNA-CMPK2 promotes HCV replication and lncRNA-CMPK2 is significantly upregulated in the primary human hepatocytes after treatment with IFNα and knockdown of lncRNA-CMPK2 exhibited a negative regulatory role in the modulation of the IFN response with the increase in the expression of several ISGs, such as Mx1, ISG15 and CXCL10 (Kambara et al., 2014) . Recently, Carnero et al found HCV infection increased the expression of lncRNA EGOT, an event that was induced by the NF-κB activated retinoic acid-inducible gene 1(RIG-I) and the RNA-activated kinase PKR. Moreover, EGOT expression was also increased after infection with influenza or Semliki Forest virus (SFV) (Carnero et al., 2016) . Although, lncRNA EGOT was found to involve in the NF-κB activated RIG-I and PKR pathway, the specific mechanisms in this pathway and antiviral response remain unclear. Additionally, lncRNA GAS5 was found to be upregulated during HCV infection in Huh7 cells and lncRNA GAS5 inhibited HCV replication by binding viral NS3 protein but the innate immune response remains low (Qian et al., 2016) .