Virus-induced lncRNA-BTX allows viral replication by regulating intracellular translocation of DHX9 and ILF3 to induce innate escape

The roles of long noncoding RNA (lncRNA) and RNA-binding proteins (RBPs) in antiviral innate response war-rant further investigation. Here, we identify an lncRNA, termed lncRNA-BTX (between Tbk1 and Xpot), which is upregulated upon viral infection via an IRF3-type I interferon-independent pathway, promoting viral innate immune escape. Deletion of lncRNA-BTX in cells or mice significantly reduces viral load in vitro or in vivo, respectively. Mechanistically, lncRNA-BTX strengthens the interactions between DHX9 or ILF3 (two RBPs that have opposite functions in regulating the replication of RNA virus) and their respective partner, JMJD6 or ILF2, which regulates intracellular translocations of DHX9 and ILF3 from the nucleus to the cyto-plasm. Put simply, lncRNA-BTX facilitates DHX9's return to the cytoplasm and retains ILF3 within the nu-cleus, promoting viral replication. This work unveils a strategy developed by the virus to bypass host innate immunity, thus providing a potential target for antiviral therapeutics.

Automated summary

A recently identified lncRNA, lncRNA-BTX, is found to promote viral replication and immune escape by enhancing the interactions between specific RBPs. This discovery unveils a strategy developed by viruses to evade host innate immunity, and provides a potential target for antiviral therapeutics.