rs3775291 C/T基因多态性与无症状人类嗜T淋巴细胞病毒1型感染中干扰素-α水平升高有关。

rs3775291 C/T polymorphism is associated with elevated IFN-α level in asymptomatic HTLV-1 infection.

作者信息

Ferreira Fabiane Dos Santos, Brito Wandrey Roberto Dos Santos, Santana Emmanuelle Giuliana Mendes, Oliveira Aline Kelly Alves, de Lima Aline Cecy Rocha, Amoras Ednelza da Silva Graça, da Costa Carlos Araujo, Souza Maísa Silva, Lima Sandra Souza, Ishak Ricardo, Cayres-Vallinoto Izaura Maria Vieira, Vallinoto Antonio Carlos Rosário, Queiroz Maria Alice Freitas

机构信息

Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.

Graduate Program in Biology of Infectious and Parasitic Agents, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.

出版信息

Front Cell Infect Microbiol. 2025 Aug 4;15:1604259. doi: 10.3389/fcimb.2025.1604259. eCollection 2025.

DOI:10.3389/fcimb.2025.1604259

PMID:40831704

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12358490/

Abstract

INTRODUCTION

Alterations in the immune response may influence the development of HTLV-1-associated diseases. TLR3 detects viral nucleic acids, including HTLV-1, and triggers the production of IFN-I and other cytokines. Genetic variations in may alter the antiviral and inflammatory responses and contribute to the progression of HTLV-1 infection. The present study investigated the association of polymorphisms in the gene (rs5743305 T/A and rs3775291 C/T) with HTLV-1 infection status and their relationship with infection-associated diseases, receptor expression levels, proviral load, and inflammatory and antiviral cytokines.

METHODS

Blood samples were collected from 179 individuals with HTLV-1 infection (82 with inflammatory diseases and 97 asymptomatic individuals) and 179 controls. Genotyping of polymorphisms, analysis of gene expression, and quantification of proviral load were performed by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA).

RESULTS

The polymorphisms showed no correlation with susceptibility to HTLV-1 infection, or the occurrence of disease symptoms linked to the infection. The presence of disease symptoms was associated with higher TNF-α levels and proviral load. rs5743305 T/A polymorphism was not associated with variations in and IFN-α levels. For the rs3775291 C/T polymorphism, asymptomatic individuals carrying the TT polymorphic genotype presented significantly higher IFN-α levels and lower proviral load. The profile of asymptomatic individuals carrying the polymorphic genotypes for rs3775291 C/T was characterized by higher levels of and IFN-α and lower levels of proviral load, TNF-α and IL-6 compared to those with the wild-type genotype.

CONCLUSION

Although polymorphisms in the TLR3 gene have not been associated with the presence of symptoms of HTLV-1-related inflammatory diseases, the rs3775291 C/T polymorphism appears to contribute to a better evolution of the HTLV-1 infection status and inflammatory process among asymptomatic individuals.

摘要

引言

免疫反应的改变可能会影响与人类嗜T淋巴细胞病毒1型（HTLV-1）相关疾病的发展。Toll样受体3（TLR3）可检测包括HTLV-1在内的病毒核酸，并触发I型干扰素（IFN-I）和其他细胞因子的产生。TLR3基因的遗传变异可能会改变抗病毒和炎症反应，并促进HTLV-1感染的进展。本研究调查了TLR3基因多态性（rs5743305 T/A和rs3775291 C/T）与HTLV-1感染状态的关联，以及它们与感染相关疾病、受体表达水平、前病毒载量以及炎症和抗病毒细胞因子的关系。

方法

采集了179例HTLV-1感染者（82例患有炎症性疾病，97例无症状个体）和179例对照者的血样。通过实时聚合酶链反应（PCR）进行多态性基因分型、TLR3基因表达分析和前病毒载量定量，并通过酶联免疫吸附测定（ELISA）测量细胞因子水平。

结果

这些多态性与HTLV-1感染的易感性或与感染相关的疾病症状的发生无关。疾病症状的出现与较高的肿瘤坏死因子-α（TNF-α）水平和前病毒载量相关。rs5743305 T/A多态性与TLR3和IFN-α水平的变化无关。对于TLR3 rs3775291 C/T多态性，携带TT多态基因型的无症状个体呈现出显著更高水平的IFN-α和更低的前病毒载量。与野生型基因型个体相比，携带TLR3 rs3775291 C/T多态基因型的无症状个体的特征是TLR3和IFN-α水平较高，前病毒载量、TNF-α和白细胞介素-6（IL-6）水平较低。