title: Role of IL-21 in HTLV-1 infections with emphasis on HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).
abstract: Interleukin-21 (IL-21) enhances the survival and cytotoxic properties of cytotoxic T cells (CTLs) and exhibits essential roles in controlling chronic viral infections. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive inflammatory disease of the nervous system. The main determinant of disease progression is efficiency of the CTL response to Human T lymphotropic virus types I (HTLV-1). In this study, the expression of host IL-21 and HTLV-I Tax and proviral load (PVL) was evaluated to understand the role and mechanism of IL-21 in HTLV-1 infections and the subsequent development of HAM/TSP. A cross-sectional study was carried out on 20 HAM/TSP patients, 20 asymptomatic HTLV-1 carriers (ACs) and 20 healthy controls (HCs) to evaluate the expression of IL-21 and Tax and PVL in non-activated and phorbol myristate acetate (PMA)-ionomycin-activated peripheral blood mononuclear cells (PBMCs). The mean mRNA expression of IL-21 in the non-activated and activated PBMCs was higher (by 5-13 times) in the HAM/TSP patients than in ACs and HCs (p < 0.05); however, there was no significant difference between ACs and HCs. In contrast to the IL-21 mRNA expression, the serum level of the IL-21 protein was significantly lower in the HAM/TSP patients than in ACs and HCs (p < 0.05). Furthermore, higher expression of Tax and PVL was observed in the HAM/TSP subjects than ACs (p < 0.05). In addition, Tax gene expression was positively correlated with PVL (R = 0.595, p = 0.000) and IL-21 gene expression (R = 0.395, p = 0.021) in the HTLV-1-infected subjects. In conclusion, the increase in IL-21 mRNA expression may reflect the attempt of infected T cells to induce an appropriate antiviral response, and the decrease in IL-21 protein expression may reflect the inhibition of IL-21 mRNA translation by viral factors in favour of virus evasion and dissemination.
authors.affiliation: Immunology Center, Inflammation and Inflammatory Diseases Research Centre, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Taraneh
authors.initials: T
authors.lastname: Rajaei
authors.affiliation: Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Farajifard
authors.affiliation: Immunology Center, Inflammation and Inflammatory Diseases Research Centre, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Houshang
authors.initials: H
authors.lastname: Rafatpanah
authors.affiliation: Department of Neurology and HTLV-1 Foundation, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Bustani
authors.affiliation: Immunology Center, Inflammation and Inflammatory Diseases Research Centre, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Narges
authors.initials: N
authors.lastname: Valizadeh
authors.affiliation: Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Bahareh
authors.initials: B
authors.lastname: Rajaei
authors.affiliation: Immunology Center, Inflammation and Inflammatory Diseases Research Centre, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran. rezaeer@mums.ac.ir.
authors.forename: Seyed Abdolrahim
authors.initials: SA
authors.lastname: Rezaee
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D016356:Gene Products, tax / Q000032:analysis*; D015490:HTLV-I Infections / Q000473:pathology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis* / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification*; D012333:RNA, Messenger / Q000032:analysis; D019562:Viral Load; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D016356:Gene Products, tax; D007378:Interleukins; D012333:RNA, Messenger; C514970:tax protein, Human T-lymphotrophic virus 1; D000098546:Interleukin-21
keywords: HAM/TSP; HTLV-1; IL-21; Proviral load; Tax