HLA-G 3'-untranslated region polymorphisms are associated with HTLV-1 infection, proviral load and HTLV-associated myelopathy/tropical spastic paraparesis development

• Published in: Journal of general virology Vol. 97; no. 10; pp. 2742 - 2752
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England 01-10-2016
• Subjects: 3' Untranslated Regions; Adolescent; Adult; Aged; Female; Genetic Predisposition to Disease; HLA-G Antigens - genetics; HLA-G Antigens - immunology; HTLV-I Infections - genetics; HTLV-I Infections - immunology; HTLV-I Infections - virology; Human T-lymphotropic virus 1 - genetics; Human T-lymphotropic virus 1 - physiology; Humans; Male; Middle Aged; Paraparesis, Tropical Spastic - genetics; Paraparesis, Tropical Spastic - immunology; Paraparesis, Tropical Spastic - virology; Polymorphism, Genetic; Proviruses - genetics; Proviruses - physiology; Retroviridae; Spinal Cord Diseases - genetics; Spinal Cord Diseases - immunology; Spinal Cord Diseases - virology; Young Adult
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/jgv.0.000559

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.