Molecular Study of HBZ and gp21 Human T Cell Leukemia Virus Type 1 Proteins Isolated from Different Clinical Profile Infected Individuals

Abstract

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.

Cytoplasmic Localization of HTLV-1 HBZ Protein: A Biomarker of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)

“…It has been recently described the existence of aminoacid variations in the HBZ protein both in asymptomatic carriers and HAM/TSP patients. These variations were identified in the activation domain and in the nuclear localization signal sequence [ 24 ]. Thus, it might be possible that HBZ sequence variation may influence the subcellular localization of the protein.…”

Molecular characterization of HTLV‐1 genomic region hbz from patients with different clinical conditions

“…These modifications can interfere in protein activity and binding connections. One example is the Y477H gp21 mutation, associated with the switch of the helix to coil structure, which modifies the secondary structure of the protein 8 . Depending on where it is located, the alteration can modify posttranslational modification sites, chemical modifications that can alter the protein conformation, localization, and function 9 …”

“…One example is the Y477H gp21 mutation, associated with the switch of the helix to coil structure, which modifies the secondary structure of the protein. 8 Depending on where it is located, the alteration can modify posttranslational modification sites, chemical modifications that can alter the protein conformation, localization, and function. 9 The molecular characterization of the viral genome can provide important information for understanding the different clinical outcomes associated with HTLV-1 infection.…”