Association of TLR3 single nucleotide polymorphisms with susceptibility to HTLV-1 infection in Iranian asymptomatic blood donors

Abstract INTRODUCTION: The human T-lymphotropic virus type 1 (HTLV-1) has a single-stranded RNA genome and expresses specific proteins that have oncogenic potential. Approximately 15 to 20 million people worldwide have been infected by this virus. Changes in protein or gene expression are the effects of single nucleotide polymorphisms (SNPs) within the Toll-like receptor 3 (TLR3) gene. The function and efficacy of signal transduction also lead to modified immune responses. The present study aimed to investigate the association of SNPs within TLR3 (rs3775291 and rs3775296) with susceptibility to HTLV-1 infection in Iranian asymptomatic blood donors. METHODS: This study was performed on 100 HTLV-1-infected asymptomatic blood donors and 118 healthy blood donors. Genomic DNA from all participants was purified and then amplified using specific PCR primers. SNPs within TLR3 were evaluated using the restriction fragmentation length polymorphism technique, and the results were analyzed using SPSS software (version 22). RESULTS: The frequencies of the TLR3 (rs3775296) CC, CA, AA genotypes were 70%, 24%, and 6% in the patient group, and 50.8%, 44.9%, and 4.2% in the control group, respectively. There was a significant difference in the frequency distribution of TLR3 (rs3775296) genotypes and alleles, but not in the frequency distribution of TLR3 (rs3775291) genotypes between the patient and control groups. CONCLUSIONS: The TLR3 SNP rs3775296 was significantly associated with HTLV-1 infection and may be a protective factor against this viral infection.

Polymorphism in the interleukin-10 gene is associated with overactive bladder phenotype associated with HTLV-1 infection

Abstract INTRODUCTION Human T-cell lymphotropic virus type 1 (HTLV-1)-associated inflammatory diseases are not well understood; however, their clinical manifestations may be influenced by the host genetic background. METHODS We genotyped 298 individuals with HTLV-1 and 380 controls for interleukin-10 (IL10) gene variants-rs3024496, rs1800871, rs1800896-and used logistic regression analysis to determine their association with clinical phenotypes. RESULTS No association with HTLV-1 infection was observed. However, allele A of rs1800896 (1082bp upstream) was associated with protection against neurological impairment, specifically overactive bladder (OR=0.447, 95% CI 0.28-0.70, p=0.001). CONCLUSIONS Our data suggests that IL10 regulation ameliorates neurological damage in HTLV-1 infections.

NLRP3 polymorphism is associated with protection against human T-lymphotropic virus 1 infection

Inter-individual heterogeneity in the response to human T-lymphotropic virus 1 (HTLV-1) infection has been partially attributed to host genetic background. The antiviral activity of the inflammasome cytoplasmic complex recognises viral molecular patterns and regulates immune responses via the activation of interleukin (IL)-1 family (IL-1, IL-18 and IL-33) members. The association between polymorphisms in the inflammasome receptors NLRP1 and NLRP3 and HTLV-1 infection was evaluated in a northeastern Brazilian population (84 HTLV-1 carriers and 155 healthy controls). NLRP3 rs10754558 G/G was associated with protection against HTLV-1 infection (p = 0.012; odds ratio = 0.37). rs10754558 affects NLRP3 mRNA stability; therefore, our results suggest that higher NLRP3 expression may augment first-line defences, leading to the effective protection against HTLV-1 infection.