Are RIG-1 and MDA5 Expressions Associated with Chronic HBV Infection?

Melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene 1 (RIG-1) as the pattern recognition receptors play important roles in viral mRNA recognition. Chronic HBV-infected (CHB) patients are unable to properly respond to hepatitis B virus (HBV). Therefore, the aim of the present study was to evaluate the mRNA levels of MDA5 and RIG-1 in the peripheral blood immune cells of CHB patients in comparison to healthy controls. In this cross-sectional study, the mRNA levels of MDA5 and RIG-1 were examined in 60 CHB patients and 60 healthy controls using the real-time polymerase chain reaction (PCR) technique. Our results showed that mRNA levels of MDA5 and RIG-1 were significantly decreased and increased, respectively, in CHB patients when compared to healthy controls. Our results also revealed that mRNA levels of MDA5 and RIG-1 were not altered among CHB patients with various states of e-antigen of hepatitis B and HBV-DNA viral loads. According to the results presented here, it may be concluded that downregulation of MDA5 may be a responsible mechanism from several reasons, which leads to HBV persistence in CHB patients.

The effect of depression and anxiety on expression levels of toll like receptor signaling molecules in chronic HBV infected patients.

BACKGROUND: Toll- like receptors (TLRs) play an important role in the recognition of DAMPs and PAMPs and induction of inflammation. Previous studies demonstrated that depression and anxiety can influence the expression levels of immune related molecules. Our previous study revealed that mRNA levels of IRAKIRAK4, TRAF3 and IRF7 were significantly decreased in chronic HBV infected (CHB) patients when compared to healthy controls. Therefore, the aim of this study was to evaluate the effects of depression and anxiety on the expression levels of these molecules in CHB patients. METHODS: Sixty CHB patients participated in this study and filled out the standard questionnaires; and the expression of IRAK4, TRAF3 and IRF7 were examined using Real-Time PCR techniques. RESULTS: The results of this study demonstrated that expression of IRAK4, TRAF3 and IRF7 did not differ between patients with various stages of depression and anxiety (all p>0.05). CONCLUSION: According to the results, it seems that declined expression of IRAK4, TRAF3 and IRF7 in CHB patients were not related to depression and anxiety, and other factors including genetic and immunoregulatory effects of HBV may be responsible for the declined expression of these molecules.

Decreased Expressions of STING but not IRF3 Molecules in Chronic HBV Infected Patients.

CONTEXT: The stimulator of interferon genes (STING) induces the activation of interferon regulatory factor 3 (IRF3) in response to intracellular viral double-stranded (ds) DNA. The aim of this study was to evaluate mRNA levels of STING and its downstream transcription factor, IRF3, in the isolated peripheral blood mononuclear cells (PBMCs) of patients with chronic HBV (CHB) infection. METHODS: This study was performed on 60 healthy controls and 60 CHB patients. The mRNA levels of STING and IRF3 were determined using Real-Time polymerase chain reaction (PCR) techniques. The SPSS software version 18 was used to analyze raw data. RESULTS: The results revealed that mRNA levels of STING were significantly decreased in CHB patients in comparison to healthy controls (P = 0.013). Our results also revealed that expression levels of IRF3 were not different between CHB patients and healthy controls (P = 0.828). CONCLUSIONS: In the present study, we found that CHB patients were unable to express appropriate levels of STING. Thus, it may result in impairment of HBV-DNA recognition and subsequently disruption of immune responses. These results suggest a plausible mechanism which may partially define the fact that immune responses are impaired in CHB patients.

The frequency of CCR5 promoter polymorphisms and CCR5 Δ 32 mutation in Iranian populations.

Evidence showed that chemokines serve as pro-migratory factors for immune cells. CCL3, CCL4 and CCL5, as the main CC chemokines subfamily members, activate immune cells through binding to CC chemokine receptor 5 or CCR5. Macrophages, NK cells and T lymphocytes express CCR5 and thus, affected CCR5 expression or functions could be associated with altered immune responses. Deletion of 32 base pairs (Δ 32) in the exon 1 of the CCR5 gene, which is known as CCR5 Δ 32 mutation causes down regulation and malfunction of the molecule. Furthermore, it has been evidenced that three polymorphisms in the promoter region of CCR5 modulate its expression. Altered CCR5 expression in microbial infection and immune related diseases have been reported by several researchers but the role of CCR5 promoter polymorphisms and CCR5 Δ 32 mutation in Iranian patients suffering from these diseases are controversial. Due to the fact that Iranian people have different genetic backgrounds compared to other ethnics, hence, CCR5 promoter polymorphisms and CCR5 32 mutation association with the diseases may be different in Iranian patients. Therefore, this review addresses the most recent information regarding the prevalence as well as association of the mutation and polymorphisms in Iranian patients with microbial infection and immune related diseases as along with normal population.

TLR3 plays significant roles against hepatitis B virus.

Hepatitis B virus (HBV) as the main prevalent infectious agent, play important roles in inducing severe liver diseases. Previous studies demonstrated that during prolonged forms of hepatitis B infection including chronic, asymptomatic and occult forms, patients are unable to eradicate HBV from hepatocytes completely. The main mechanisms responsible for development of the forms of hepatitis B are yet to be identified. Investigators suggested that the various genetic and immunological parameters of the patients may are responsible for resulting in the prolonged infection forms. It has been evidenced that TLRs play key roles in inducing appropriate immune responses, against viral infections. Therefore, these molecules can be considered as crucial sensors for HBV detection to induce immune responses against this virus. It has also been documented that the TLR3 detects intracellular viral dsRNA and subsequently activates NF-κB via the TRIF pathway. Therefore, impaired TLR3 expression may result in inappropriate immune responses against HBV which is reported in prolonged forms of hepatitis B. This review collected the recent information regarding the important roles of TLR3 in immune responses against HBV and also the status of TLR3 expression and its genetic variations in prolonged forms of HBV infections.

Important roles played by TGF-ß in hepatitis B infection.

Hepatitis B virus (HBV) which includes, fulminant, acute, chronic, asymptomatic, and occult HBV infection is the most prevalent virus that leads to human liver diseases. Chronic, asymptomatic, and occult infection can induce further sever diseases such as hepatocellular carcinoma (HCC) and cirrhosis of the liver. The underlying mechanisms that allow progression of the prolonged forms of the infection and subsequent HCC or cirrhosis of the liver are yet to be clarified. However, many researchers have suggested that immunological and genetic parameters may play important roles in the etiology of hepatitis B. Transforming growth factor beta (TGF-ß) is an important cytokine with dual regulatory functions in the immune system and in the responses against viral infections. However, the pathways and mechanisms controlling these are not fully understood. The crucial roles of TGF-ß in the development of Th17 and T regulatory lymphocytes, the main cell types involved in autoimmunity and destructive immune related diseases, have been documented and this provides insights into TGF-ß function during hepatitis infection and subsequent HCC and cirrhosis of the liver. Recent findings also confirm that TGF-ß directly alters hepatocyte function during hepatitis B, hence, the aim of this review is to address the current data regarding the association and status of TGF-ß with hepatitis B infection and its related disorders including HCC and cirrhosis of the liver.

Decreased expression of toll like receptor signaling molecules in chronic HBV infected patients.

INTRODUCTION: Toll like receptors (TLRs) and their signaling molecules play important roles in microbe recognition and induction of immune responses, including production of inflammatory cytokines, against viral infections. Therefore, the aim of this study was to examine expression levels of TLR signaling molecules (IRAK1, IRAK4, TRAF3, and IRF7) and the pro-inflammatory cytokines, IL-12 and IL-6 in chronic HBV infected (CHB) patients. DESIGN: This study was performed on 60 CHB patients and 60 healthy controls and the expression of IRAK1, IRAK4, TRAF3, and IRF7 and their downstream inflammatory cytokines (IL-12 and IL-6) were evaluated by Real-Time PCR and ELISA techniques. RESULTS: The results demonstrated that expression of IRAK4, TRAF3, and IRF7 were significantly decreased in PBMCs of CHB patients in comparison to healthy controls. Serum levels of IL-12 were significantly increased, while, IL-6 were not differ between patients and controls. CONCLUSIONS: Based on the results presented here it seems that CHB patients do not express appropriate levels of the genes in the TLRs pathway which may lead to impaired immune responses against HBV infection which is seen in the patients.