LncRNAs in the Type I Interferon Antiviral Response

Abstract

The proper functioning of the immune system requires a robust control over a delicate equilibrium between an ineffective response and immune overactivation. Poor responses to viral insults may lead to chronic or overwhelming infection, whereas unrestrained activation can cause autoimmune diseases and cancer. Control over the magnitude and duration of the antiviral immune response is exerted by a finely tuned positive or negative regulation at the DNA, RNA, and protein level of members of the type I interferon (IFN) signaling pathways and on the expression and activity of antiviral and proinflammatory factors. As summarized in this review, committed research during the last decade has shown that several of these processes are exquisitely regulated by long non-coding RNAs (lncRNAs), transcripts with poor coding capacity, but highly versatile functions. After infection, viruses, and the antiviral response they trigger, deregulate the expression of a subset of specific lncRNAs that function to promote or repress viral replication by inactivating or potentiating the antiviral response, respectively. These IFN-related lncRNAs are also highly tissue- and cell-type-specific, rendering them as promising biomarkers or therapeutic candidates to modulate specific stages of the antiviral immune response with fewer adverse effects.

Keywords: LncRNAs; antiviral response; type I IFN.

Figure 1

Long non-coding RNA (LncRNA) classification according to their genomic context relative to protein-coding genes (PCGs) and their regulatory DNA elements. See text for details.

Figure 2

LncRNAs affect protein activity directly or by regulating transcriptional and post-transcriptional processes in the nucleus (on the left) or in the cytoplasm (on the right). These effects result from the ability of lncRNAs to form primary, secondary, and tertiary structures able to bind DNA, RNA, or proteins. See text for details. Blue arrows depict activation while the red arrows, inhibition.

Figure 3

LncRNAs affect many steps of the interferon (IFN) synthesis (left) and signaling pathways (right). See text for details. LncRNA-linked blue arrows depict activation while red arrows indicate inhibition. Name frames are in blue for activating lncRNAs, red for inhibitory lncRNAs, and in both colors for lncRNAs with dual functions.