TLR3 rs3775291C/T polymorphism is associated with elevated IFN-α level in asymptomatic HTLV-1 infection

Fabiane dos Santos Ferreira¹Wandrey Brito¹Emmanuelle Giuliana Mendes Santana¹Aline Kelly Alves Oliveira¹Aline Lima¹Ednelza da Silva Graça Amoras¹Carlos Araujo Da Costa²Maísa Silva de Sousa²Sandra Souza Lima¹Ricardo Ishak¹Izaura M.V. Cayres-Vallinoto¹Antonio C. R. Vallinoto¹Maria Alice Freitas Queiroz^1*

• ¹Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil
• ²Laboratory of Cellular and Molecular Biology, Tropical Medicine Center, Federal University of Pará, Belém, Pará, Brazil

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 TLR3 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 TLR3 gene (rs5743305T/A and rs3775291C/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 TLR3 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. TLR3 rs5743305T/A polymorphism was not associated with variations in TLR3 and IFN-α levels. For the TLR3 rs3775291C/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 TLR3 rs3775291C/T was characterized by higher levels of TLR3 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 TLR3 rs3775291C/T polymorphism appears to contribute to a better evolution of the HTLV-1 infection status and inflammatory process among asymptomatic individuals.