IFIT1

The purpose of the study was to construct the potential diagnostic model of immune-related genes during the development of heart failure caused by idiopathic dilated cardiomyopathy.

GSE5406 and GSE57338 were downloaded from the GEO website ( https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/geo/ ). CIBERSORT was used for the evaluation of immune infiltration in idiopathic dilated cardiomyopathy (DCM) of GSE5406. Differently expressed genes were calculated by the limma R package and visualized by the volcano plot. The immune-related genes were downloaded from Immport, TISIDB, and InnateDB. Then the immune-related differential genes (IRDGs) were acquired from the intersection. Protein-protein interaction network (PPI) and Cytoscape were used to visualize the hub genes. Three machine learning methods such as random forest, logical regression, and elastic network regression model were adopted to construct the prediction model. The diagnostic value was also validated in GSE57338.

Our study demonstrated the obvious different ratio of T cell CD4 memory activated, T cell regulatory Tregs, and neutrophils between DCM and control donors. As many as 2139 differential genes and 274 immune-related different genes were identified. These genes were mainly enriched in lipid and atherosclerosis, human cytomegalovirus infection, and cytokine-cytokine receptor interaction. At the same time, as many as fifteen hub genes were identified as the IRDGs (IFITM3, IFITM2, IFITM1, IFIT3, IFIT1, HLA-A, HLA-B, HLA-C, ADAR, STAT1, SAMHD1, RSAD2, MX1, ISG20, IRF2). Moreover, we also discovered that the elastic network and logistic regression models had a higher diagnostic value than that of random forest models based on these hub genes.

Our study demonstrated the pivotal role of immune function during the development of heart failure caused by DCM. This study may offer new opportunities for the detection and intervention of immune-related DCM.

Alphaviruses can replicate in arthropods and in many vertebrate species including humankind, but only in vertebrate cells do infections with these viruses result in a strong inhibition of host translation and transcription. Translation shutoff by alphaviruses is a multifactorial process that involves both host- and virus-induced mechanisms, and some of them are not completely understood. Alphavirus genomes contain cis-acting elements (RNA structures and dinucleotide composition) and encode protein activities that promote the translational and transcriptional resistance to type I IFN-induced antiviral effectors. Among them, IFIT1, ZAP and PKR have played a relevant role in alphavirus evolution, since they have promoted the emergence of multiple viral evasion mechanisms at the translational level. In this review, we will discuss how the adaptations of alphaviruses to vertebrate hosts likely involved the acquisition of new features in viral mRNAs and proteins to overcome the effect of type I IFN.

ATP synthase inhibitory factor 1 (ATPIF1) can activate mitochondrial autophagic pathway and mediates immune response by regulating ATP synthase activity. However, the role of fish ATPIF1 on viral infection is still unknown. In this study, we identified an ATPIF1 homolog (Ec-ATPIF1) from orange-spotted grouper (Epinephelus coioides). Ec-ATPIF1 is mainly expressed in the kidney and liver. The expression of Ec-ATPIF1 was significantly up-regulated after RGNNV stimulation in vitro. Further experiments showed that overexpression of Ec-ATPIF1 inhibited the expression of viral genes (CP and RdRp) and intracellular ATP synthesis. Ec-ATPIF1 overexpression also promoted the expression of mitophagy related genes (PINK1, Parkin, BNIP3, NIX, FUNDC1, LC3), inflammation-related factors (IL-1β, IL-6, IL-8, IL-10, TNF-α, TLR2) and interferon pathway factors (IRF1, IRF3, IRF7, MX1, ISG15, ISG56, MDA5, TRIF). While the knockdown of Ec-ATPIF1 exhibited the opposite effects on the expression of viral genes and immune-related factors above. These data suggest that Ec-ATPIF1 can impact viral infection by regulating mitophagy, ATP synthesis, the expression of inflammatory factors and interferon pathway factors. These findings will be beneficial to better explore the immune regulatory mechanisms of fish respond to viral infection.