Original Article

Molecular epidemiology and phylogenetic analysis of human T-lymphotropic virus type 1 in the tax gene and it association with adult t-cell leukemia/lymphoma disorders


Background and Objectives: Human T-lymphotropic virus type-1 (HTLV-1) belongs to retrovirus family that causes the neurological disorder HTLV-1 adult T-cell leukemia/lymphoma (ATLL). Since 1980, seven subtypes of the virus have been recognized. HTLV-1 is prevalent and endemic in some regions, such as Africa, Japan, South America and Iran as the endemic regions of the HTLV-1 in the Middle East. To study HTLV-1 subtypes and routes of virus spread in Iran, phylogenetic and phylodynamic analyses were performed and for as much as no previous phylogenetic studies were conducted in Tehran, we do this survey. To this purpose, the Tax region of HTLV-1 was used.
Materials and Methods: In this study 100 samples were collected from blood donors in Tehran. All samples were screened for anti-HTLV-I antibodies by ELISA. Then, genomic DNA was extracted from all positive samples (10 people), and for confirmation of infection, ordinary PCR was performed for both the HBZ and LTR regions. Moreover, the Tax region was amplified and purified PCR products were sequenced and analyzed, and finally, a phylogenetic tree was constructed using Mega X software.
Results: Phylogenetic analysis confirmed that isolates from Iran, Japan, Brazil, and Africa are located within the extensive ‘‘transcontinental’’ subgroup A clade of HTLV-1 Cosmopolitan subtype a. The Japanese sequences are the closest to the Iranian sequences and have the most genetic similarity with them.
Conclusion: Through phylogenetic and phylodynamic analyses HTLV-1 strain in Tehran were characterized in Iran. The appearance of HTLV-1 in Iran was probably happened by the ancient Silk Road which linked China to Antioch.

1. Rafatpanah H, Farid R, Golanbar G, Jabbari Azad F. HTLV-I infection: virus structure, immune response to the virus and genetic association studies in HTLV-I-infected individuals. Iran J Allergy Asthma Immunol 2006;5: 153-166.
2. Saffar S, Azadmanesh K, Golmohammadi T, Golkar M, Amminian M, Mirshahabi H, et al. Production of recombinant human T lymphotropic virus type 1 Tax protein in Rosetta (DE3) bacterial host. J Param Sci 2010;1: 35-42.
3. Ahmadi Ghezeldasht S, Shirdel A, Assarehzadegan MA, Hassannia T, Rahimi H, Miri R, et al. Human T lymphotropic virus type I (HTLV-I) oncogenesis: molecular aspects of virus and host interactions in pathogenesis of adult T cell leukemia/lymphoma (ATL). Iran J Basic Med Sci 2013;16: 179-195.
4. Acheson NH (2007). Fundamentals of molecular virology. 2nd ed. Wiley. New York.
5. Fogarty KH, Zhang W, Grigsby IF, Johnson JL, Chen Y, Mueller JD, et al. New insights into HTLV-1 particle structure, assembly, and Gag-Gag interactions in living cells. Viruses 2011;3: 770-793.
6. Cook LB, Elemans M, Rowan AG, Asquith B. HTLV-1: persistence and pathogenesis. Virology 2013;435: 131-140.
7. Boxus M, Willems L. Mechanisms of HTLV-1 persistence and transformation. Br J Cancer 2009;101: 1497-1501.
8. Rafatpanah H, Farid Hosseini R, Pourseyed SH. The impact of immune response on HTLV-I in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Iran J Basic Med Sci 2013;16: 235-241.
9. Farid Hosseni R, Jabbari F, Shabestari M, Rezaee SA, Gharivani Y, Valizadeh N, et al. Human T lymphotropic virus type I (HTLV-I) is a risk factor for coronary artery disease. Iran J Basic Med Sci 2013;16: 217-220.
10. Shoeibi A, Etemadi M, Moghaddam Ahmadi A, Amini M, Boostani R. "HTLV-I infection" twenty-year research in neurology department of Mashhad university of medical sciences. Iran J Basic Med Sci 2013;16: 202-207.
11. Akbarin MM, Rahimi H, Hassannia T, Shoja Razavi G, Sabet F, Shirdel A. Comparison of HTLV-I proviral load in adult T cell leukemia/lymphoma (ATL), HTLV-I-associated myelopathy (HAM-TSP) and healthy carriers. Iran J Basic Med Sci 2013;16: 208-212.
12. Hedayati-Moghaddam MR. A systematic review for estimation of HTLV-I infection in the blood donors of Iran. Iran J Basic Med Sci 2013;16: 196-201.
13. Kadas J, Boross P, Weber IT, Bagossi P, Matuz K, Tozser J. C-terminal residues of mature human T-lymphotropic virus type 1 protease are critical for dimerization and catalytic activity. Biochem J 2008;416: 357-364.
14. Futsch N, Mahieux R, Dutartre H. HTLV-1, the other pathogenic yet neglected human retrovirus: from transmission to therapeutic treatment. Viruses 2017;10:1.
15. Stienlauf S, Yahalom V, Schwartz E, Shinar E, Segal G, Sidi Y. Epidemiology of human T-cell lymphotropic virus type 1 infection in blood donors, Israel. Emerg Infect Dis 2009;15: 1116-1118.
16. Kchour G, Rezaee R, Farid R, Ghantous A, Rafatpanah H, Tarhini M, et al. The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma. Retrovirology 2013;10: 91.
17. Martin JL, Maldonado JO, Mueller JD, Zhang W, Mansky LM. Molecular studies of HTLV-1 replication: an update. Viruses 2016;8: 31.
18. Azran I, Schavinsky-Khrapunsky Y, Aboud M. Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity. Retrovirology 2004;1: 20.
19. Hall WW, Fujii M. Deregulation of cell-signaling pathways in HTLV-1 infection. Oncogene 2005;24: 5965-5975.
20. Matsuoka M, Yasunaga JI. Human T-cell leukemia virus type 1: replication, proliferation and propagation by Tax and HTLV-1 bZIP factor. Curr Opin Virol 2013;3: 684-691.
21. Romanelli MG, Diani E, Bergamo E, Casoli C, Ciminale V, Bex F, et al. Highlights on distinctive structural and functional properties of HTLV Tax proteins. Front Microbiol 2013;4: 271.
22. Grassmann R, Aboud M, Jeang KT. Molecular mechanisms of cellular transformation by HTLV-1 Tax. Oncogene 2005;24: 5976-5985.
23. Stoppa G, Rumiato E, Saggioro D. Ras signaling contributes to survival of human T-cell leukemia/lymphoma virus type 1 (HTLV-1) Tax-positive T-cells. Apoptosis 2012;17: 219-228.
24. Ciminale V, Rende F, Bertazzoni U, Romanelli MG. HTLV-1 and HTLV-2: highly similar viruses with distinct oncogenic properties. Front Microbiol 2014;5: 398.
25. Fujikawa D, Nakagawa S, Hori M, Kurokawa N, Soejima A, Nakano K, et al. Polycomb-dependent epigenetic landscape in adult T-cell leukemia. Blood 2016; 127: 1790-1802.
26. Gligorijevic V, Przulj N. Methods for biological data integration: perspectives and challenges. J R Soc Interface 2015;12: 20150571.
27. Kawaguchi A, Orba Y, Kimura T, Iha H, Ogata M, Tsuji T, et al. Inhibition of the SDF-1alpha-CXCR4 axis by the CXCR4 antagonist AMD3100 suppresses the migration of cultured cells from ATL patients and murine lymphoblastoid cells from HTLV-I Tax transgenic mice. Blood 2009;114: 2961-2968.
28. Yamagishi M, Nakano K, Miyake A, Yamochi T, Kagami Y, Tsutsumi A, et al. Polycomb-mediated loss of miR-31 activates NIK-dependent NF- κB pathway in adult T cell leukemia and other cancers. Cancer cell 2012;21: 121-134.
29. Rahman S, Quann K, Pandya D, Singh S, Khan ZK, Jain P. HTLV-1 Tax mediated downregulation of miRNAs associated with chromatin remodeling factors in T cells with stably integrated viral promoter. PLoS One 2012;7(4): e34490.
30. Sfetcu O, Gauci AA (2015). Geographical distribution of areas with a high prevalence of HTLV-1 infection. Stockholm: ECDC.
31. Afonso PV, Cassar O, Gessain A. Molecular epidemiology, genetic variability and evolution of HTLV‑1 with special emphasis on African genotypes. Retrovirology 2019;16: 39.
32. Pineda M, Bouzas MB, Golemba M, Remesar M, Aulicino P, Mammana L, et al. Molecular epidemiology of HTLV-1 in Argentina. Retrovirology 2015;12(Suppl 1): P85.
33. Ngoma AM, Mutombo PB, Omokoko MD, Mvika ES, Nollet KE, Ohto H. Prevalence and molecular epidemiology of human T-lymphotropic virus type 1 among women attending antenatal clinics in Sub-Saharan Africa: a systematic review and meta-analysis. Am J Trop Med Hyg 2019;101: 908-915.
34. de Almeida Rego FF, Mota–Miranda A, de Souza Santos E, Galva˜ o–Castro B, Alcantara LC. Seroprevalence and molecular epidemiology of HTLV-1 isolates from HIV-1 co-infected women in Feira de Santana, Bahia, Brazil. AIDS Res Hum Retroviruses 2010;26: 1333-1339.
IssueVol 13 No 4 (2021) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijm.v13i4.6976
Human T-lymphotropic virus type-1; Adult T cell leukemia lymphoma; Phylogenetic; Phylodynamic; Iran

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How to Cite
Pourrezaei S, Shadabi S, Gheidishahran M, Rahimiforoushani A, Akhbari M, Tavakoli M, Safavi M, Madihi M, Norouzi M. Molecular epidemiology and phylogenetic analysis of human T-lymphotropic virus type 1 in the tax gene and it association with adult t-cell leukemia/lymphoma disorders. Iran J Microbiol. 2021;13(4):509-517.