Cilião Alves Daiani Cristina, Haddad Rodrigo, Rocha-Júnior Maurício Cristiano, de Deus Wagatsuma Virgínia Mara, Martelli-Palomino Gustavo, Marques Adriana Aparecida, Takayanagui Osvaldo Massaiti, Covas Dimas Tadeu, Kashima Simone, Donadi Eduardo Antônio
Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14049-900, Brazil.
Faculdade de Ceilândia, Universidade de Brasília (UnB), Brasília, Distrito Federal CEP: 72220-900, Brazil.
J Gen Virol. 2016 Oct;97(10):2742-2752. doi: 10.1099/jgv.0.000559. Epub 2016 Jul 22.
Most human T-lymphotropic virus type 1 (HTLV-1)-infected patients remain asymptomatic throughout life. The factors associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development have not been fully elucidated; immunological and genetic factors may be involved. The association of 14 bp INS/DEL HLA-G polymorphism with HTLV-1 infection susceptibility has been reported previously. Here, other polymorphic sites at the HLA-G 3'-UTR (14-bp D/I, +3003C/T, +3010C/G, +3027A/C, +3035C/T, +3142C/G, +3187A/G and +3196C/G) were evaluated in 37 HTLV-1-infected individuals exhibiting HAM/TSP, 45 HTLV-1 asymptomatic carriers (HAC) and 153 uninfected individuals, followed up at University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil. It was observed that: (i) 14bpDI genotype is a risk factor for HTLV-1 infection, while the 14bpDD and +3142CC genotypes were associated with protection against infection; (ii) the +3142C allele and the +3003CT and +3142CC genotypes were associated with susceptibility, while 14bpII and +3003TT genotypes were associated with protection against HAM/TSP development; and (iii) the 14bpII, +3010CC, +3142GG and +3187AA genotypes were associated with lower HTLV-1 proviral load compared to respective counterpart genotypes. Findings that HLA-G has a well-recognized immunomodulatory role and that the genetic variability at HLA-G 3'-UTR may post-transcriptionally modify HLA-G production indicate a differential genetic susceptibility to: (i) the development of HTLV-1 infection, (ii) the magnitude of HTLV-1 proviral load and (iii) HAM/TSP development.
大多数1型人类嗜T淋巴细胞病毒（HTLV-1）感染患者终生无症状。与HTLV-1相关脊髓病/热带痉挛性截瘫（HAM/TSP）发展相关的因素尚未完全阐明；免疫和遗传因素可能参与其中。先前已有报道14bp INS/DEL HLA-G多态性与HTLV-1感染易感性的关联。在此，对巴西圣保罗大学里贝朗普雷图医学院大学医院随访的37例表现为HAM/TSP的HTLV-1感染个体、45例HTLV-1无症状携带者（HAC）和153例未感染个体，评估了HLA-G 3'-UTR的其他多态性位点（14bp D/I、+3003C/T、+3010C/G、+3027A/C、+3035C/T、+3142C/G、+3187A/G和+3196C/G）。观察到：（i）14bpDI基因型是HTLV-1感染的危险因素，而14bpDD和+3142CC基因型与预防感染相关；（ii）+3142C等位基因以及+3003CT和+3142CC基因型与易感性相关，而14bpII和+3003TT基因型与预防HAM/TSP发展相关；（iii）与各自对应的基因型相比，14bpII、+3010CC、+3142GG和+3187AA基因型与较低的HTLV-1前病毒载量相关。HLA-G具有公认的免疫调节作用以及HLA-G 3'-UTR的遗传变异性可能在转录后修饰HLA-G产生的这些发现表明，在以下方面存在不同的遗传易感性：（i）HTLV-1感染的发展，（ii）HTLV-1前病毒载量的大小，以及（iii）HAM/TSP的发展。
