title: Interleukin-18 and interferon-gamma polymorphisms are implicated on proviral load and susceptibility to human T-lymphotropic virus type 1 infection.
abstract: Interleukin-18 (IL-18) and interferon-gamma (IFN-γ) exert important functions in both innate and adaptive immune responses against intracellular pathogens and viruses. Previous studies suggested that host genetic factors, including cytokines gene polymorphisms, could be involved in the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Thus, we analyzed -137C/G and -607A/C of the IL-18 promoter and +874T/A of the IFN-γ in DNA samples from 98 HTLV-1-infected individuals exhibiting or not clinical symptoms and 150 healthy control individuals. The IL-18 promoter -607CC genotype was significantly lower in HTLV-1 asymptomatic carriers (HAC) and HTLV-1-infected individuals (HAC + HAM/TSP) than healthy control group. In contrast, the -607AC genotype was significantly higher in HAC and HTLV-1-infected individuals group compared to the healthy control group. The -137G/-607A IL-18 haplotype was higher in infected group than healthy control group, and the -137C/-607C IL-18 haplotype was increased in the healthy control group compared to the others. Finally, the IFN-γ polymorphism analysis showed that the HTLV-1-infected individuals with +874AT genotype presented higher proviral load than +874AA genotype. These data indicate that the IL-18-607AC genotype and -137G/-607A haplotype could be a risk factor for HTLV-1 infection, whereas the protective effect could be conferred by -607CC genotype and -137C/-607C haplotype. Also, the IFN-γ could be implicated on the proviral load levels.
authors.affiliation: Hemocentro de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14051-140, Brazil.
authors.forename: M C
authors.initials: MC
authors.lastname: Rocha-Júnior
authors.forename: R
authors.initials: R
authors.lastname: Haddad
authors.forename: D C
authors.initials: DC
authors.lastname: Cilião Alves
authors.forename: V M
authors.initials: VM
authors.lastname: de Deus Wagatsuma
authors.forename: C T
authors.initials: CT
authors.lastname: Mendes-Junior
authors.forename: N H S
authors.initials: NH
authors.lastname: Deghaide
authors.forename: O M
authors.initials: OM
authors.lastname: Takayanagui
authors.forename: D T
authors.initials: DT
authors.lastname: Covas
authors.forename: E A
authors.initials: EA
authors.lastname: Donadi
authors.forename: S
authors.initials: S
authors.lastname: Kashima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005787:Gene Frequency; D006239:Haplotypes; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000235:genetics* / Q000276:immunology / Q000821:virology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011533:Proviruses; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D019562:Viral Load
chemical_list: D020382:Interleukin-18; D007371:Interferon-gamma