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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 (HCV) is a single stranded RNA virus. It affects millions of people worldwide and is considered as a leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. A recent study reported that TLR4 gene polymorphisms are good prognostic predictors and are associated with protection from liver fibrosis among Caucasians. This study aims to investigate the implication of genetic polymorphisms of TLR4 gene on the HCV infection in Saudi Arabian patients. Two SNPs in the TLR4 gene, rs4986790 (A/G) and rs4986791 (C/T), were genotyped in 450 HCV patients and 600 uninfected controls. The association analysis confirmed that both SNPs showed a significant difference in their distribution between HCV-infected patients and uninfected control subjects (P<0.0001; OR=0.404, 95% CI=0.281–0.581) and (P<0.0001; OR=0.298, 95% CI=0.201–0.443), respectively. More importantly, haplotype analysis revealed that four haplotypes, AC, GT, GC, and AT (rs4986790, rs4986791), were significantly associated with HCV infection when compared with control subjects. One haplotype AC was more prominently found when chronic HCV-infected patients were compared with cirrhosis/HCC patients (frequency = 94.7% and P=0.04). Both TLR4 SNPs under investigation were found to be significantly implicated with HCV-infection among Saudi Arabian population.

Recent studies have demonstrated that polymorphisms near the interleukin-28B (IL-28B) gene could predict the response to Peg-IFN-a/RBV combination therapy in HCV-infected patients. The aim of the study was to correlate the serum level of IL28B in HCV-infected patients with virus genotype/subgenotype and disease progression. IL28B serum level was detected and variations at five single nucleotide polymorphisms (SNPs) in IL28B gene region were genotyped and analyzed. The variation of IL28B genetic polymorphisms was found to be strongly associated with HCV infection when healthy control group was compared to HCV-infected patients with all P values <0.0001. Functional analysis revealed that subjects carrying rs8099917-GG genotype had higher serum level of IL28B than those with GT or TT genotypes (P=0.04). Also, patients who were presented with cirrhosis (Cirr) only or with cirrhosis plus hepatocellular carcinoma (Cirr+HCC) had higher levels of serum IL28B when compared to chronic HCV-infected patients (P=0.005 and 0.003, resp.). No significant association was found when serum levels of IL28B were compared to virus genotypes/subgenotypes. This study indicates that variation at SNP rs8099917 could predict the serum levels of IL28B in HCV-infected patients. Furthermore, IL28B serum level may serve as a useful marker for the development of HCV-associated sequelae.

Introduction: In early 2009, a novel influenza A (H1N1) virus appeared in Mexico and rapidly disseminated worldwide. Little is known about the phylogeny and evolutionary dynamics of the H1N1 strain found in Saudi Arabia. Methodology: Nucleotide sequencing and bioinformatics analyses were used to study molecular variation between the virus isolates. Results: In this report, 72 hemagglutinin (HA) and 45 neuraminidase (NA) H1N1 virus gene sequences, isolated in 2009 from various regions of Saudi Arabia, were analyzed. Genetic characterization indicated that viruses from two different clades, 6 and 7, were circulating in the region, with clade 7, the most widely circulating H1N1 clade globally in 2009, being predominant. Sequence analysis of the HA and NA genes revealed a high degree of sequence identity with the corresponding genes from viruses circulating in the South East Asia region and with the A/California/7/2009 strain. New mutations in the HA gene of pandemic H1N1 (pH1N1) viruses, that could alter viral fitness, were identified. Relaxed-clock and Bayesian Skyline Plot analyses, based on the isolates used in this study and closely related globally representative strains, indicated marginally higher substitution rates than the type strain (5.14×10-3 and 4.18×10-3 substitutions/nucleotide/year in the HA and NA genes, respectively). Conclusions: The Saudi isolates were antigenically homogeneous and closely related to the prototype vaccine strain A/California/7/2009. The antigenic site of the HA gene had acquired novel mutations in some isolates, making continued monitoring of these viruses vital for the identification of potentially highly virulent and drug resistant variants.

Introduction: Saudi Arabia (SA) experienced a highly pathogenic avian influenza (HPAI) H5N1 outbreak in domesticated birds in 2007. Methodology: Forty-three hemagglutinin (HA) and 41 neuraminidase (NA) genes of HPAI H5N1 viruses were sequenced and phylogenetic analyses of completely sequenced genes were performed to compare with other viral HA and NA gene sequences available in the public databases. Results: Molecular characterization of the H5N1 viruses revealed two genetically distinct clades, 2.2.2 and 2.3.1, of H5N1 viruses circulating in the area. Amino acid sequence analysis of the HA gene indicated that the virus from 2.2.2 contained the sequence SPQGERRRK-R/G at the cleavage site, while the virus from 2.3.1 contained the sequence SPQRERRRK-R/G. Additionally, a few mutations with amino acid substitutions such as M226I at N-link glycosylation site were identified in two of these isolates. Amino acid sequence of the NA gene showed a 20-amino-acid deletion in the NA stalk region, required for enhanced virulence of influenza viruses and its adaptation from wild birds to domestic chickens. As close contact between humans and birds is unavoidable, there is a need for a thorough understanding of the virus epidemiology, factors affecting the spread of the virus, and molecular characterization such as phylogeny and substitution rates of H5N1 viruses circulating in the region. Conclusion: Two genetically distinct clades were found to be circulating in the country, which could likely result in recombination and emergence of more virulent viral strains. These findings could be helpful for the authorities devising control measures against these viruses.