Association of the p75NTR Ser205Leu Polymorphism with Asymptomatic HTLV-1 Infection

Viruses. 2022 May 28;14(6):1175. doi: 10.3390/v14061175.

Abstract

Genetic variations in components of the immune response seem to be an important factor that contributes to the manifestation of symptoms of some diseases related to HTLV-1 infection. Nerve growth factor (NGF) and the p75 neurotrophin receptor (p75NTR) are related to the maintenance of neurons and the activation of the immune response. In this study, we evaluated the association of the NGF -198C/T, NGF Ala35Val, and p75NTR Ser205Leu polymorphisms with HTLV-1 infection and plasma cytokine levels in 166 samples from individuals infected with HTLV-1 (59 symptomatic and 107 asymptomatic). The genotyping and quantification of the proviral load were performed by real-time PCR, and cytokine levels were measured by ELISA. The NGF -198C/T and NGF Ala35Val polymorphisms were not associated with HTLV-1 infection. The frequency of the Ser/Leu genotype of p75NTR Ser205Leu was more frequent in the control group (p = 0.0385), and the Ser/Leu genotype and allele Leu were more frequent among the asymptomatic (p < 0.05), especially with respect to the HTLV-1-associated myelopathy (HAM) group (p < 0.05). The symptomatic showed a higher proviral load and higher TNF-α and IL-10 levels (p < 0.05). Asymptomatic carriers of the Ser/Leu genotype (p = 0.0797) had lower levels of proviral load and higher levels of TNF-α (p = 0.0507). Based on the results obtained, we conclude that the p75NTR Ser205Leu polymorphism may be associated with reduced susceptibility to HTLV-1 infection, a lower risk of developing symptoms, including HAM, and better infection control.

Keywords: HAM; HTLV-1; NGF; cytokines; p75NTR; polymorphisms; proviral load.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines
  • HTLV-I Infections*
  • Human T-lymphotropic virus 1* / genetics
  • Humans
  • Nerve Growth Factor
  • Paraparesis, Tropical Spastic*
  • Proviruses / genetics
  • Receptor, Nerve Growth Factor
  • Tumor Necrosis Factor-alpha
  • Viral Load

Substances

  • Cytokines
  • Receptor, Nerve Growth Factor
  • Tumor Necrosis Factor-alpha
  • Nerve Growth Factor

Grants and funding

This research was funded by the Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPQ (grants #480128/2013-8, #312979/2018-5, #301869/2017-0) and by the Federal University of Para (PROPESP/PAPQ/2022).