Source: School of Life Sciences
Written by: Shaochun Yuan
Edited by: Wang Dongmei

The innate immune system is the first line of host defense against pathogen invasion. Upon viral infection, virus-derived nucleic acids are mainly sensed by cytosolic nucleic acid sensors, such as cGAS, RIG-I and MDA5. Recently, to identify new nucleic acid recognition receptors, and explore the differences between these receptors in terms of recognition mechanisms, cell localization or immune effects are one of the hot topics in innate immunity.

A research article entitled “Mitochondria-localised ZNFX1 functions as a dsRNA sensor to initiate antiviral responses through MAVS” has been published online in Nature Cell Biology, the top journal in cell biology, on Nov 4th, 2019. Post-doctor Yao Wang, Prof. Shaochun Yuan and Associate Research Fellow Xin Jia are the co-first authors. Prof. Anlong Xu is the corresponding author. This study revealed that ZNFX1, an interferon (IFN)-stimulated and mitochondrial-localised dsRNA sensor specifically restricts the replication of RNA viruses. ZNFX1 can initiate IFN and ISG expression immediately upon RNA virus infection by sensing viral RNAs through its Armadillo-type fold and P-loop domain and then interacts with mitochondrial antiviral signalling protein MAVS without depending on RLRs. Since ZNFX1 can initiate IFN and ISG expression at an early stage of RNA virus infection, it may serve as a positively regulated loop of the well-known RLR signaling, which provides another new layer to understand the complexity of antiviral immunity.

Besides ZNFX1, Xu's team also found another evolutionary conserved dsRNA sensor, named as DDX23 this year. By cross-species analyses, the research group found that DDX23 is mainly localized in the nucleus and can be translocated from the nucleus to the cytoplasm after viral infection. After recognizing viral dsRNA, DDX23 triggers type I IFN and ISGs expression, which positively regulates the RIG-I-dependent antiviral signaling pathway. The related result was published on Frontiers in Immunology on September 18th, 2019. Pro. Shaochun Yuan and Anlong Xu are the co-corresponding authors.

Access to these papers:
https://www.nature.com/articles/s41556-019-0416-0
https://www.frontiersin.org/articles/10.3389/fimmu.2019.02202/full