Differential expression of viral pathogen-associated molecular pattern receptors mRNA in Egyptian chronic hepatitis C virus patients

Abstract

Abstract Background One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host’s innate immune surveillance is modification of its pathogen-associated molecular patterns (PAMPs) by altering or hiding its RNA which interfering with toll-like receptors (TLRs) signaling and ultimately hindering the production of proinflammatory cytokines, chemokines, and interferons (IFNs). This study aimed to examine the expression levels of TLR3, TLR7, and IFN-α to investigate the correlated expression pattern among them in chronic HCV patients. Patients included in this study were categorized into two different groups, non-treated chronic HCV patients and treated chronic HCV patients, in addition to healthy volunteers as a control group. The blood samples were assessed for HCVAb, HCVRNA, HCV genotypes, and different biochemical analyses. The mRNA levels of TLR3, TLR7, and IFN-α in peripheral blood of chronic HCV patients were quantitatively measured in comparison to healthy controls. Results The expression levels of TLR3, TLR7, and IFN-α were significantly downregulated in non-treated chronic HCV patients compared to both treated HCV patients and control subjects. On the other hand, treated HCV patients showed non-significant downregulation of the same three sensing receptors (TLR3, TLR7, and IFN-α) compared to control group. Obviously, the expression levels of IFN-α were positively correlated with the levels of both TLR3 and TLR7. Conclusion The exhausted innate immunity against HCV may correlate to HCV downregulation of TLR3 and TLR7 expression on innate immune cells with a subsequent decrease in INF-α production and the possibility of targeting these receptors to enhance the immune response and clear the infection needs further studies.

Keywords

• Hepatitis C virus
• TLR3 and TLR7 signaling
• IFN-α transcription