Human T cell leukemia virus type 1 (HTLV-1) is associated with a neurological syndrome named tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM) and the disease progression involves viral factors. The gp21 glycoprotein is involved in envelope trafficking and membrane targeting while the bZIP protein is indispensable for cell growth and proliferation. This study aimed to assess the molecular diversity of gp21 and HBZ proteins in TSP/HAM and healthy carriers. DNA samples from HTLV-1-infected individuals were submitted to PCR and sequencing, and the molecular analyses were performed using bioinformatics tools. From eight gp21-analyzed sequences one amino acid change (Y477H) was associated with the switch of a helix to coil structure at secondary structure prediction. From 10 HBZ analyzed sequences, two amino acid changes were identified (S9P and T95I) at the activation domain. One mutation (R112C) located at the nuclear localization signal was present in 66.7% and 25% of healthy carriers (HC) and TSP/HAM groups, respectively. This is the first report of mutations in the HBZ region. These polymorphisms might be important for viral fitness.
The HTLV-1 gp21 glycoprotein is involved in envelope trafficking and membrane targeting while bZIP protein is indispensable for cell growth and proliferation. This study aimed to assess the molecular diversity of gp21 and HBZ proteins, in TSP/HAM and healthy carriers. DNA samples from HTLV-1 infected individuals were submitted to PCR, sequencing, and the molecular analyses were performed using bioinformatics tools. From eight gp21 analyzed sequences one amino acid change (Y477H) was associated to the switch of helix to coil structure at secondary structure prediction. From ten HBZ analyzed sequences, two amino acid changes were identified (S9P and T95I) at the activation domain. One mutation (R112C) located at nuclear localization signal was present in 66.7% and 25% of HC and TSP/HAM groups, respectively. This is the first report of mutations in HBZ region. These polymorphisms might be important for viral fitness.
The present study attempts to assess the molecular diversity of gp46 glycoprotein in HAM/TSP patients and Health Carrier (HC) individuals. The median HTLV-1 proviral load of HC (n=5) and HAM/TSP (n=5) patients was similar (average 316,227 copies/106 PBMCs). The gp46 molecular characterization of 146 clones (70 HC and 76 HAM/TSP) revealed an overall diversity, within HC and HAM/TSP clones, of 0.4% and 0.6%, respectively. A single amino acid (aa) substitution (S35L) was exclusive for the HC group, and three gp46 substitutions (F14S, N42H, G72S) were exclusive for the HAM/TSP group. The remaining frequent mutation (V247I) was present in both groups (p = 0.0014). The in silico protein analysis revealed that the mutated alleles F14S and N42H represent more hydrophilic and flexible protein domains that are likely to be less antigenic. The Receptor Binding Domain is quite variable in the HAM/TSP group. Two other domains (aa 53-75 and 175-209) that contain multiple linear T-cell epitopes showed genetic diversity in both HAM/TSP and HC groups. Further analysis revealed 27 and 13 T-cell epitopes for class I HLA alleles and class II HLA alleles, when analyzing the entire gp46. We still cannot associate any of the gp46 found mutations with the clinical profile.
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