Potential Relevance of Cytoplasmic Viral Sensors and Related Regulators Involving Innate Immunity in Antiviral Response

Targeted impairment of innate antiviral responses in the liver of chronic hepatitis C patients

“…Consequently, the low mRNA levels of IFNb, IL28A/B, IL29, and CCL5, which expressions are strictly dependent on the main transcriptional activators IRF3 and NF-jB activated during the early antiviral response, are indicative of a severe impairment of the early host defense in these chronically HCV-infected patients. In parallel, we also observed a global diminution of CARDIF total amount as previously reported [29], and CARDIF cleavage associated to high level of NS3/4A protein expression. Dixit et al recently demonstrated that peroxisomal CARDIF could be responsible for a strong but transient expression of ISGs in the absence of any secreted IFN, in contrast to the traditional mitochondrial located CARDIF responsible for the antiviral response [30].…”

Selective IgA Deficiency in Autoimmune Diseases

“…Together with retinoic acid-inducible gene I (RIG-1), it functions as a sensor for viral infections. IFIH1 expression is highly upregulated in activated immune cells in response to type 1 interferon induced by viral infections, suggesting that it could potentially be involved in the pathogenesis of autoimmune diseases including T1D (187). Several SNPs within the IFIH1 gene and its 3′ untranslated region show an association with T1D (rs2111485, rs13422767, rs1990760 and rs3747517) (188), where the rs1990760 marker (Ala946Thr) is the most strongly associated (reviewed in [189]).…”

Predictors of Virological Response to a Combination Therapy with Pegylated Interferon Plus Ribavirin Including Virus and Host Factors

“…Both virus- and host-related elements have been reported as factors correlated to therapeutic effects of combination therapy [11–13]. A particular focus has been placed on virus mutations, age, gender, fibrosis of the liver, lipid metabolism, and degree of fatty metamorphosis of the liver.…”

“…Asahina et al reported that liver biopsies were performed before the PEG-IFN and RBV combination therapy to examine the correlation between the gene expression involved in innate immunity and the therapeutic effects, and in the patients in whom RIG-I expression is high and the expression of Cardif, an adaptor gene, is low, it was found that there are many nonresponders (NVRs) in which HCVRNA does not become negative during the course of treatment [13]. It was therefore revealed that there are many NVRs among the patients in whom the ratio of RIG-I to Cardif in liver tissue is high and that this ratio is low in the SVR patients.…”