Article
Polymorphisms in HTLV-1 Tax-responsive elements in HTLV- 1-associated myelopathy/tropical spastic paraparesis patients are associated with reduced proviral load but not with disease progression
Registro en:
GOMES, Yago Côrtes Pinheiro et al. Polymorphisms in HTLV-1 Tax-responsive elements in HTLV-1-associated myelopathy/tropical spastic paraparesis patients are associated with reduced proviral load but not with disease progression. The Journal of general virology, v. 102, n. 9, p. 1-11, 2021
0022-1317
10.1099/jgv.0.001649
Autor
Gomes, Yago Côrtes Pinheiro
Silva, Marcus Tulius Teixeira
Leite, Ana Claudia Celestino Bezerra
Lima, Marco Antonio Sales Dantas
Araújo, Abelardo Queiroz Campos
Silva Filho, Isaac Lima
Vicente, Ana Carolina Paulo
Espíndola, Otávio de Melo
Resumen
Human T-lymphotropic virus type 1 (HTLV-1) provirus expression is mainly directed by Tax-responsive elements (TRE) within the long terminal repeats (LTR). Mutations in TRE can reduce provirus expression and since a high proviral load (PVL) is a risk factor for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we evaluated polymorphisms in the 5' LTR and the association with PVL and disease progression. HTLV-1 LTR and tax sequences derived from asymptomatic carriers (AC) and HAM/TSP patients followed in a longitudinal study were analysed according to PVL and clinical severity. Individuals infected with HTLV-1 presenting the canonical TRE, considering strain ATK-1 as the consensus, displayed sustained higher PVL. By contrast, an LTR A125G mutation in TRE was associated with slightly reduced PVL only in HAM/TSP patients, although it did not influence the speed of disease progression. Moreover, this polymorphism was frequent in Latin American strains of the HTLV-1 Cosmopolitan Transcontinental subtype. Therefore, polymorphisms in the 5' TRE of HTLV-1 may represent one of the factors influencing PVL in HAM/TSP patients, especially in the Latin American population. Indeed, higher PVL in the peripheral blood has been associated with an increased inflammatory activity in the spinal cord and to a poorer prognosis in HAM/TSP. However, this event was not associated with TRE polymorphisms.