HLA-G 14-bp Insertion/Deletion Polymorphism Is a Risk Factor for HTLV-1 Infection

Abstract

About 95% of HTLV-1 infected patients remain asymptomatic throughout life, and the risk factors associated with the development of related diseases, such as HAM/TSP and ATL, are not fully understood. The human leukocyte antigen-G molecule (HLA-G), a nonclassical HLA class I molecule encoded by MHC, is expressed in several pathological conditions, including viral infection, and is related to immunosuppressive effects that allow the virus-infected cells to escape the antiviral defense of the host. The 14-bp insertion/deletion polymorphism of exon 8 HLA-G gene influences the stability of the transcripts and could be related to HTLV-1-infected cell protection and to the increase of proviral load. The present study analyzed by conventional PCR the 14-bp insertion/deletion polymorphism of exon 8 HLA-G gene in 150 unrelated healthy subjects, 82 HTLV-1 infected patients with symptoms (33 ATL and 49 HAM), and 56 asymptomatic HTLV-1 infected patients (HAC). In addition, the proviral load was determined by quantitative real-time PCR in all infected groups and correlated with 14-bp insertion/deletion genotypes. The heterozygote genotype frequencies were significantly higher in HAM, in the symptomatic group, and in infected patients compared to control (p < 0.05). The proviral load was higher in the symptomatic group than the HAC group (p < 0.0005). The comparison of proviral load and genotypes showed that -14-bp/-14-bp genotype had a higher proviral load than +14-bp/-14-bp and +14-bp/+14-bp genotypes. Although HLA-G 14-bp polymorphism does not appear to be associated with HTLV-1 related disease development, it could be a genetic risk factor for susceptibility to infection.

Association of HLA-G alleles and 3′ UTR 14 bp haplotypes with recurrent miscarriage in Brazilian couples

“…Therefore, determined haplotypic combinations of HLA-G alleles and presence or absence of the 14 bp segment could predispose women to RM. These findings also may open new doors in the understanding of the association of HLA-G alleles and 3=UTR 14 bp haplotypes with several disorders, such as susceptibility to virus infection or tumors progression, as evidence shows that 14 bp polymorphism at 3= UTR of could be a genetic risk factor for susceptibility to HTLV-1, human CMV, vertical transmission of HIV, and the development of cervical cancer after human papillomavirus infection [61][62][63][64].…”

Leukotrienes Are Upregulated and Associated with Human T-Lymphotropic Virus Type 1 (HTLV-1)-Associated Neuroinflammatory Disease

“…HTLV-1 proviral load was quantified as previously described [49]. Genomic DNA samples isolated from peripheral blood of the HTLV-1 infected individuals were used to perform quantitative RT-PCR with the SYBR Green system (Applied Biosystems).…”

Role of 14-Bp HLA-G, INDEL Polymorphism in Recurrent Miscarriage

“…In different populations, the polymorphic sites in the 3′ UTR are organized into several haplotypes, with each of them being associated with group or a single of promoter region and coding polymorphisms, thus form extended HLA-G haplotypes that result in altered expression of HLA-G mRNA and thus protein isoforms (Kolte et al, 2010). The14-bp INDELpolymorphism is suggested to perform the following functions: 1) Transcripts containing the 14-bp fragment may undergo an additional splicing step in which this sequence may act as a cryptic branch point and result in the alternative splicing of HLA-G mRNA to remove 92 bases from this region (Haddad et al 2011). Deletion of this sequence may affect mRNA stability.…”