• Letter to Editor
    The Unique Molecular Structure of Human T-Cell Leukemia Virus Type 1 Protease
    Mohsen Karbalaei1 and Masoud Keikha2*
    1Department of Microbiology and Virology, Jiroft University of Medical Sciences, Iran
    2Department of Microbiology and Virology, Mashhad University of Medical Sciences, Iran
    *Corresponding author: Masoud Keikha, Department of Microbiology and Virology, Mashhad University of Medical Sciences, Mashhad, Iran, Tel: 09386836425; Email: masoud.keykha90@gmail.com
    Submitted: 23 April 2019; Accepted: 29 April 2019; Published: 30 April 2019
    Cite this article: Karbalaei M, Keikha M (2019) The Unique Molecular Structure of Human T-Cell Leukemia Virus Type 1 Protease. JSMC Biochem Mol Res 1: 2.
  • Letter to Editor
    Human T-cell leukemia virus type 1 (HTLV-1) is retrovirus type C which causative agent of Human T-cell leukemia virus type 1 associated myelopathy/tropical spastic paraparesis (HAM/ TSP), Adult T-cell leukemia/lymphoma (ATL or ATLL), uveitis, arthritis, alveolitis/bronchiectasis, dermatitis, and lymphadenitis [1]. There are approximately 15-20 million people were infected by HTLV-1 that majority of them where lives in HTLV-1 endemic area including North America, Central Africa, Caribbean islands, Japan, Australia and Iran (particularly Khorasan province) [1-2]. Although more than 90% of the HTLV-1 infected individuals are remains as asymptomatic carrier but 2-6% of HTLV-1infected individuals are progress to ATLL, as well as 2-3% develop to HAM/TSP [3].
    HTLV-1 is transmitted by unsafe sexually contact, injection, blood transfusion and breastfeeding throughout population [2,3]. There is no selective treatment option against HTLV-1; combination of AZT plus INF-α is only available therapeutic option of HTLV-1 infection which has not efficient completely [4]. It is suggested that molecular targeting of HTLV-1 has considered as the best strategy for appropriate treatment; of which, the Protease enzyme is the suitable option because of its play key role in process of HTLV-1 polyprotein and has critical role in HTLV-1 pathogenesis [5]. Therefore, molecular targeting of HTLV-1 protease has one of the interest option for development of selective antiviral compounds against HTLV-1 [3,5]. But it’s necessary to making a survive about structural conformation and sequence dissimilarities between different strains of HTLV-1 to design therapeutic option based on the conserved domains of HTLV-1 Protease which inhibits all strains of HTLV- 1. Therefore, the of this study was comparative analysis and molecular structure study of the HTLV-1 Protease molecules for determination of dissimilarities and conserved domains of HTLV- 1 protease for construct of selective HTLV-1 protease inhibitors.
    Initially, total of 100 HTLV-1 protease amino acid sequences of different regions were obtained from NCBI (https://www. ncbi.nlm.nih.gov/protein); then multiple alignment and the phylogenic tree was constructed using the neighbor-joining method with Kimura‐2‐parameter (K2P) distance for evaluation of genetic diverge among HTLV-1 strains. According to our results, multiple alignment study (via ClustalW) was showed that highest similarity in the sequence of HTLV-1 Protease among different HTLV-1 strains (100-98.93% similarity); also, the phylogenic tree was approved the majority of similarity in target gene sequences (Figure 1).
    • Figure 1:The Phylogenetic tree of the one hundred sequences of HTLV-1 protease using the neighbor joining method. View Figure

    Subsequently, the crystal structure of HTLV-1 protease was obtained from PDB (3WSJ) for determination of active site (Figure 2). Then, entirely of the crystal structures of HTLV-1 Protease were obtained from PDB (https://www.rcsb.org/) and multiple aligned in order to discovery of dissimilarity of the sequences (Figure 3). We confirmed that amino acid sequence of the active site of HTLV-1 is nearly conserved complete among different HTLV-1 strains.
    • Figure 2:The active site of HTLV-1 Protease was highlighted in the crystal structure and amino acid sequence. View Figure

    • Figure 3:Multiple alignment of HTLV-1 Protease sequences. View Figure

    Finally, about 100 crystal structure of HTLV-1 Protease were superimposed for 3D dimensional and conformation analysis of the HTLV-1 Protease molecule which showed that a strong similarity among HTLV-1 Protease structures and confirmed our previous results about homology of HTLV-1 Protease in different strains (Figure 4).
    • Figure 4:The superimposed of one hundred crystal structure of HTLV-1 Protease. View Figure

    Overall, HTLV-1 protease is aspartic protease which responsible for maturation hydrolysis of HTLV-1 polyproteins throughout active site includes two aspartic acid residues (Asp32, 36), it’s expressed in homodimeric form with each chain consisting of 125 residues that is highly specific to its substrate [6]. In recently years, the HTLV-1 Protease is known as the suitable molecular targets for efficiently treatment of HTLV-1 infection. According to us survive, the active site of the HTLV-1 Protease is conserved among different strains of HTLV-1 and can be used as target for development of HTLV-1 Protease inhibitors.
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