Influence of Immunogenetic Biomarkers in the Clinical Outcome of HTLV-1 Infected Persons

Abstract

Human T-lymphotropic virus 1, a member of the Retroviridae family, causes a neglected, silent, persistent infection affecting circa 5 to 10 million people around the world, with biology, immune pathology, clinical diseases, epidemiology, and laboratory issues still unsolved. Most of the infected subjects are asymptomatic, but severe clinical disorders appear as a neurodegenerative disease (HTLV-1 associated myelopathy—HAM) or a lymphoprolipherative disorder (Adult T Leukemia/Lymphoma—ATLL) and in other target organs of the human body. HTLV-1 infections are frequently asymptomatic, but there is a large spectrum of diseases that have been described along the years. The mechanisms by which the virus interacts with the host, the different modes of response of the host to the infection, and the immunogenic characteristics of the host are some of the interesting and unanswered questions that may direct the outcome of the disease. The most relevant published results dealing with the genetic variations of the host, the immune response to HTLV-1 infection, and the outcome of the infection are presented herein, including Human Leucocyte Antigen (HLA), Killer Immunoglobulin-like Receptors (KIR), interleukin 6, 10, 28, Fas and Fas ligand, IFN-gamma, TNF-A, and Mannose-binding lectin. In summary, there are still several unmet research needs in the field of useful biomarkers on HTLV-1 pathogenesis.

NK cells and monocytes modulate primary HTLV-1 infection

“…Chronic HTLV-1 infection is associated with unrelenting immune activation accompanied by high levels of both pro- and anti-inflammatory cytokines [ 80 , 81 ]. This outcome likely results from the host’s continuous, albeit unsuccessful, attempts to eradicate viral infection and maintain tissue homeostasis [ 82 ].…”

Immunopathogenesis and Cellular Interactions in Human T-Cell Leukemia Virus Type 1 Associated Myelopathy/Tropical Spastic Paraparesis

“…For example, the protective effects of HLA-A ∗ 02:07 and HLA-C ∗ 08 and the detrimental effects of HLA-B ∗ 54 has been demonstrated in southern Japan ( Boelen et al, 2018 ). HLA-Cw ∗ 08 was similarly seen in both ACs and HAM / TSP patients in a Brazilian study, but was associated with a protective effect in Japan and higher susceptibility to HAM/TSP in Iran ( Vallinoto et al, 2019 ). Class II HLA-DRB1 ∗ 0101 has been identified as a predisposing factor to the disease in Japan, Iran, and Spain and it has been shown that the effect is exacerbated in the absence of the protective effect of HLA-A ∗ 02 ( Jeffery et al, 1999 ; Saito, 2019 ; Vallinoto et al, 2019 ).…”

“…HLA-Cw ∗ 08 was similarly seen in both ACs and HAM / TSP patients in a Brazilian study, but was associated with a protective effect in Japan and higher susceptibility to HAM/TSP in Iran ( Vallinoto et al, 2019 ). Class II HLA-DRB1 ∗ 0101 has been identified as a predisposing factor to the disease in Japan, Iran, and Spain and it has been shown that the effect is exacerbated in the absence of the protective effect of HLA-A ∗ 02 ( Jeffery et al, 1999 ; Saito, 2019 ; Vallinoto et al, 2019 ). Haplotype HLA-B ∗ 0702-Cw ∗ 0702-DRB1 ∗ 0101-DQB1 ∗ 0501 is also predisposing in the absence of HLA-A ∗ 02 ( Catalan-Soares et al, 2009 ).…”

“…Haplotype HLA-B ∗ 0702-Cw ∗ 0702-DRB1 ∗ 0101-DQB1 ∗ 0501 is also predisposing in the absence of HLA-A ∗ 02 ( Catalan-Soares et al, 2009 ). In addition, the protective effects of HLA-B ∗ 07 in Spain and HLA-A ∗ 0201 and HLA-Cw ∗ 0801 in Japan are documented as well ( Vallinoto et al, 2019 ). The predisposing effects HLA-B ∗ 5401 have been proven, but are not observed in Brazil ( Catalan-Soares et al, 2009 ; Bangham et al, 2015 ; Enose-Akahata and Jacobson, 2019 ).…”

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

“…Viruses 2022, 14, 1175 2 of 11 have been the focus of several studies in the search for biomarkers that can explain the evolution of infection and the development of associated diseases. Genetic variations in genes encoding cytokines, restriction factors, and proteins that activate apoptosis have been associated with the development of HAM and other inflammatory manifestations associated with HTLV-1 [9][10][11][12][13][14].…”