Association of Toll-Like Receptor 3 Single-Nucleotide Polymorphisms and Hepatitis C Virus Infection

Abstract

Toll-like receptor 3 (TLR3) plays a key role in innate immunity by recognizing pathogenic, double-stranded RNAs. Thus, activation of TLR3 is a major factor in antiviral defense and tumor eradication. Although downregulation of TLR3 gene expression has been mainly reported in patients infected with hepatitis C virus (HCV), the influence of TLR3 genotype on the risk of HCV infection, HCV-related cirrhosis, and/or hepatocellular carcinoma (HCC) remains to be determined. Single-nucleotide polymorphisms (SNPs) within the TLR3 gene and their associations with HCV-related disease risk were investigated in a Saudi Arabian population in this study. Eight TLR3 SNPs were analyzed in 563 patients with HCV, which consisted of 437 patients with chronic HCV infections, 88 with HCV-induced liver cirrhosis, and 38 with HCC. A total of 599 healthy control subjects were recruited to the study. Among the eight TLR3 SNPs studied, the rs78726532 SNP was strongly associated with HCV infection when compared to that in healthy control subjects. The rs5743314 was also strongly associated with HCV-related liver disease progression (cirrhosis and HCC). In summary, these results indicate that distinct genetic variants of TLR3 SNPs are associated with HCV infection and HCV-mediated liver disease progression in the Saudi Arabian population.

Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

“…Eradication of HCV infection involves coordinated effort between innate and adoptive immunity, as the innate immune responses initially, and later adaptive immunity becomes operational 8 weeks post‐infection . Initially, innate immunity recognises HCV via pattern recognition receptors (PRR) through TLRs, which target pathogen‐associated molecular patterns (PAMPs) found on HCV, thus augmenting immunity through upregulating IFN secretion and induction of IFN‐α‐inducible genes involved in antiviral and immune regulatory functions. The association of TLR with virological response to peg‐IFN plus RBV therapy in HCV‐infected patients explains the appearance of TLR4 and TLR2 as the top 10 treatment response related genes (Table ).…”

Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans

“…Patients with impaired TLR3-mediated responses show an elevated susceptibility to Herpes Simplex-1 Virus (HSV-1)-mediated encephalitis by encoding TLR3-deficient alleles [102,103], or by encoding deficient TRAF3, TBK1 and TRIF molecules, leading to impaired TLR-3 signaling [104][105][106]. In a Saudi Arabian population, the TLR3 rs78726532 SNP was strongly associated with Hepatitis B (HBV) and Hepatitis C (HCV) virus infections when compared to that in healthy control subjects [107,108]. The TLR3 rs5743314 C allele was also associated with HCV-related liver disease progression (cirrhosis and hepatocellular carcinoma) [107].…”

“…In a Saudi Arabian population, the TLR3 rs78726532 SNP was strongly associated with Hepatitis B (HBV) and Hepatitis C (HCV) virus infections when compared to that in healthy control subjects [107,108]. The TLR3 rs5743314 C allele was also associated with HCV-related liver disease progression (cirrhosis and hepatocellular carcinoma) [107]. However, the functional effects of these SNPs seem to be unknown.…”

Genetic variants in IFIH1 and DDX58 influence hepatitis C virus clearance in Chinese Han population

“…Previous studies demonstrated that genetic factors play an important role in HCV infection, in addition to some well‐understood factors such as age and liver function . A significant association was found between HCV infection and gene polymorphisms in immune‐related genes, such as interleukin‐family, toll‐like receptor (TLR), patatin‐like phospholipase domain containing 3, interferon lambda 4, and inosine triphosphate pyrophosphatase . Given the important biological function of RLRs in HCV infection, it is essential to explore the potential influence between RLR gene polymorphisms and HCV infection.…”

“…12 A significant association was found between HCV infection and gene polymorphisms in immune-related genes, such as interleukin-family, toll-like receptor (TLR), patatin-like phospholipase domain containing 3, interferon lambda 4, and inosine triphosphate pyrophosphatase. [13][14][15][16][17][18][19][20][21][22] Given the important biological function of RLRs in HCV infection, it is essential to explore the potential influence between RLR gene polymorphisms and HCV infection. However, research on the association between mutations in RLR-related genes and HCV infection are scant currently.…”