Molecular Characterization and Expression Analysis of SKIV Infection of Interferon-Induced Protein with Tetratricopeptide Repeats 1(IFIT1) in Epinephelus lanceolatus

Interferon-induced protein with tetratricopeptide repeats 1(IFIT1), also known as interferon-induced protein 56(IFI56) or Interferon-stimulated protein 56(ISG56), was originally identified as a protein induced upon treatment with interferon and inhibited by viral replication and translational initiation. In this study, Epinephelus lanceolatus IFIT1(ELIFIT1) gene was cloned for the first time. The complete cDNA of El IFIT1 gene includes 2921 nucleotides, and encodes a 437-amino acid(AA) protein. The putative ELIFIT1 protein has 9 TRP domains and is highly similar with IFIT1 proteins in other teleosts. In healthy fish, ELIFIT1 gene was highly expressed in the blood, which indicate its specific function in the peripheral immune system. Its expression was also observed in various immunity-related tissues including spleen, intestine, and kidney, Inducted with spotted knifejaw iridovirus(SKIV), ELIFIT1 gene expression was upregulated in the spleen, kidney, and liver 24 h after induction and reached its peak at 72 h, indicating that ELIFIT1 may play an important role in antivirus. These findings contribute to the understanding of the antiviral regulation of ELIFIT1 gene in teleost.

Interferon-induced protein with tetratricopeptide repeats 1(IFIT1) polymorphism as a genetic marker of cerebral malaria in Thai population

Objective:To know whether the effect of interferon-induced protein with tetratricopeptide repeats(IFIT)1 polymorphism influences the susceptibility of cerebral malaria outcome.Methods:Case-control association study was performed among 314 Thai patients(110 with cerebral malaria and 204 with uncomplicated malaria)infected with Plasmodium falciparum.Genotyping for five tag-single nucleotide polymorphisms of IFIT1 was performed by endpoint genotyping.Results:Genotype frequencies of all tag-SNPs(single nucleotide polymorphisms)showed no association with malaria outcome.However,C allele of rs11203109 was associated with the protection from cerebral malaria(OR=0.62,95%CI=0.38-0.99,P=0.048).Two single nucleotide polymorphisms(rs5786868 and rs57941432)were in linkage disequilibrium with rs11203109.Conclusions:This suggests that our associated single nucleotide polymorphism(rs11203109)might be a genetic marker of cerebral malaria progression in the Thai population.

Tetratricopeptide repeat domain 36 deficiency mitigates renal tubular injury by inhibiting TGF-β1-induced epithelialemesenchymal transition in a mouse model of chronic kidney disease

The damage of proximal tubular epithelial cells(PTECs)is considered a central event in the pathogenesis of chronic kidney disease(CKD)and deregulated repair processes of PTECs result in epithelialemesenchymal transition(EMT),which in turn aggravates tubular injury and kidney fibrosis.In this study,we firstly revealed that the reduction of TTC36 is associated with unilateral ureteral obstruction(UUO)-induced CKD;besides,ablation of TTC36 attenuated tubular injury and subsequent EMT in UUO-treated mice kidneys.Consistently,TTC36 overexpression promoted EMT in TGF-β1-induced HK2 cells.Moreover,TTC36 elevated the protein expression of CEBPB,which was involved in the regulation of TGF-β/SMAD3 signaling,and augmented SMAD3 signaling and downstream genetic response were reduced by CEBPB silencing.Collectively,our results uncovered that TTC36 deficiency plays a protective role in tubular injury and renal fibrosis triggered by UUO;further,TTC36 overexpression exacerbated TGF-β/SMAD3 signaling via elevating the stability of SMAD3 and CEBPB,suggesting that TTC36 inhibition may be a potential strategy in the therapy of obstructive nephropathy.

Evaluation of IFIT3 and ORM1 as Biomarkers for Discriminating Active Tuberculosis from Latent Infection

Objective Current commercially available immunological tests cannot be used for discriminating active tuberculosis(TB)from latent TB infection.To evaluate the value of biomarker candidates in the diagnosis of active TB,this study aimed to identify differentially expressed genes in peripheral blood mononuclear cells(PBMCs)between patients with active TB and individuals with latent TB infection by transcriptome sequencing.Methods The differentially expressed genes in unstimulated PBMCs and in Mycobacterium tuberculosis(Mtb)antigen-stimulated PBMCs from patients with active TB and individuals with latent TB infection were identified by transcriptome sequencing.Selected candidate genes were evaluated in cohorts consisting of 110 patients with TB,30 individuals with latent TB infections,and 50 healthy controls by quantitative real-time RT-PCR.Receiver operating characteristic(ROC)curve analysis was performed to calculate the diagnostic value of the biomarker candidates.Results Among the differentially expressed genes in PBMCs without Mtb antigen stimulation,interferon-induced protein with tetratricopeptide repeats 3(IFIT3)had the highest area under curve(AUC)value(0.918,95%CI:0.852-0.984,P<0.0001)in discriminating patients with active TB from individuals with latent TB infection,with a sensitivity of 91.86%and a specificity of 84.00%.In Mtb antigen-stimulated PBMCs,orosomucoid 1(ORM1)had a high AUC value(0.833,95%CI:0.752-0.915,P<0.0001),with a sensitivity of 81.94%and a specificity of 70.00%.Conclusion IFIT3 and ORM1 might be potential biomarkers for discriminating active TB from latent TB infection.