Skip to main content

Advertisement

Log in

A significant association between CXCL10 -1447 A > G and IL18 -607 C > A gene polymorphism with human T-cell lymphotropic virus type 1 associated myelopathy/tropical spastic paraparesis (HAM-TSP), a case-control report from city of Mashhad, Iran

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Human T-cell lymphotropic virus type 1 (HTLV-1) is the first isolated retrovirus from humans, and 2–3% of infected individuals suffer from HTLV-1 associated myelopathy tropical spastic paraparesis (HAM-TSP). Previous studies indicated that the risk of HAM-TSP could be correlated with the individuals’ genetic alterations. Mashhad is one of the areas infected with HTLV-1 in Iran. This study designed to examine the association between several important gene polymorphisms and HAM-TSP. Genotypes of 232 samples from controls, HTLV-1 carriers, and HAM-TSP patients were examined for FAS-670 (A > G), CXCL10-1447 (A > G), Foxp3-3279 (C > A), IL-18 -137 (C > G), and IL-18 -607 (C > A) gene polymorphisms by different polymerase chain reaction (PCR) techniques. A non-significant association was observed between FAS-670 A > G, Foxp3-3279 C > A, and IL-18 -137 C > G gene polymorphisms and HAM-TSP. Nevertheless, a significant (P < 0.001) association between CXCL10-1447 A > G and IL-18 -607 C > A gene polymorphisms with HAM-TSP was observed in our study population. As previous studies revealed that the CXCL10 level in the cerebrospinal fluid of HAM-TSP patients was associated with the disease progression, and as we noticed, a direct association was observed between CXCL10-1447 A > G polymorphism and HAM-TSP. These polymorphisms might be recommended as a valuable prediction criterion for the severity of the disease. The contradiction between our findings and other studies regarding IL-18 -607 C > A gene polymorphism might be associated with various factors such as genotypes frequency in diverse races and population heterogeneity in the city of Mashhad.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

The data obtained in this study are accessible from the corresponding author after well-reasoned and valid request.

References

  • Araya N, Sato T, Ando H, Tomaru U, Yoshida M, Coler-Reilly A, Yagishita N, Yamauchi J, Hasegawa A, Kannagi M, Hasegawa Y, Takahashi K, Kunitomo Y, Tanaka Y, Nakajima T, Nishioka K, Utsunomiya A, Jacobson S, Yamano Y (2014) HTLV-1 induces a Th1-like state in CD4+CCR4+ T cells. J Clin Invest 124:3431–3442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Assone T, Paiva A, Fonseca LA, Casseb J (2016) Genetic Markers of the Host in Persons Living with HTLV-1. HIV and HCV Infections, Viruses, p 8

    Google Scholar 

  • Azimi N, Nagai M, Jacobson S, Waldmann TA (2001) IL-15 plays a major role in the persistence of Tax-specific CD8 cells in HAM/TSP patients. Proc Natl Acad Sci U S A 98:14559–14564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bai M, He X, He Y, Yuan D, Jin T, Wang L (2019) IL-7R gene polymorphisms among patients with rheumatoid arthritis: a case-control study. Mol Genet Genomic Med 7:e00738

    Article  PubMed  PubMed Central  Google Scholar 

  • Bolufer P, Collado M, Barragan E, Cervera J, Calasanz MJ, Colomer D, Roman-Gomez J, Sanz MA (2007) The potential effect of gender in combination with common genetic polymorphisms of drug-metabolizing enzymes on the risk of developing acute leukemia. Haematologica 92:308–314

    Article  CAS  PubMed  Google Scholar 

  • Enose-Akahata Y, Vellucci A, Jacobson S (2017) Role of HTLV-1 Tax and HBZ in the pathogenesis of HAM/TSP. Front Microbiol 8:2563

    Article  PubMed  PubMed Central  Google Scholar 

  • Eusebio-Ponce E, Anguita E, Paulino-Ramirez R, Candel FJ (2019) HTLV-1 infection: an emerging risk. Pathogenesis, epidemiology, diagnosis and associated diseases. Rev Esp Quimioter 32:485–496

    CAS  PubMed  PubMed Central  Google Scholar 

  • Futsch N, Prates G, Mahieux R, Casseb J, Dutartre H (2018) Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases. Viruses 10.

  • Gessain A, Cassar O (2012) Epidemiological aspects and world distribution of HTLV-1 infection. Front Microbiol 3:388

    Article  PubMed  PubMed Central  Google Scholar 

  • Goncalves DU, Proietti FA, Ribas JG, Araujo MG, Pinheiro SR, Guedes AC, Carneiro-Proietti AB (2010) Epidemiology, treatment, and prevention of human T-cell leukemia virus type 1-associated diseases. Clin Microbiol Rev 23:577–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inoue N, Watanabe M, Morita M, Tomizawa R, Akamizu T, Tatsumi K, Hidaka Y, Iwatani Y (2010) Association of functional polymorphisms related to the transcriptional level of FOXP3 with prognosis of autoimmune thyroid diseases. Clin Exp Immunol 162:402–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeffery KJ, Usuku K, Hall SE, Matsumoto W, Taylor GP, Procter J, Bunce M, Ogg GS, Welsh KI, Weber JN, Lloyd AL, Nowak MA, Nagai M, Kodama D, Izumo S, Osame M, Bangham CR (1999) HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy. Proc Natl Acad Sci U S A 96:3848–3853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeffery KJ, Siddiqui AA, Bunce M, Lloyd AL, Vine AM, Witkover AD, Izumo S, Usuku K, Welsh KI, Osame M, Bangham CR (2000) The influence of HLA class I alleles and heterozygosity on the outcome of human T cell lymphotropic virus type I infection. J Immunol 165:7278–7284

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Li D, Tsun A, Li B (2015) FOXP3+ regulatory T cells and their functional regulation. Cell Mol Immunol 12:558–565

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu MT, Keirstead HS, Lane TE (2001) Neutralization of the chemokine CXCL10 reduces inflammatory cell invasion and demyelination and improves neurological function in a viral model of multiple sclerosis. J Immunol 167:4091–4097

    Article  CAS  PubMed  Google Scholar 

  • Lu L, Barbi J, Pan F (2017) The regulation of immune tolerance by FOXP3. Nat Rev Immunol 17:703–717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manohar K, Suneetha PV, Sukriti PNT, Gupta AC, Hissar S, Sakhuja P, Sarin SK (2009) Association of IL-18 promoter polymorphism with liver disease severity in HCV-infected patients. Hepatol Int 3:371–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuura E, Nozuma S, Tashiro Y, Kubota R, Izumo S, Takashima H (2016) HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP): a comparative study to identify factors that influence disease progression. J Neurol Sci 371:112–116

    Article  CAS  PubMed  Google Scholar 

  • Mohammadi A, Tajik N, Shah-Hosseini A, Alavian SM, Sharifi Z, Jarahi L (2015) FAS and FAS-ligand promoter polymorphisms in hepatitis B virus infection. Hepat Mon 15:e26490

    Article  PubMed  PubMed Central  Google Scholar 

  • Mozhgani SH, Jahantigh HR, Rafatpanah H, Valizadeh N, Mohammadi A, Basharkhah S, Rezaee SA (2018) Interferon Lambda family along with HTLV-1 proviral load, Tax, and HBZ implicated in the pathogenesis of myelopathy/tropical spastic paraparesis. Neurodegener Dis 18:150–155

    Article  CAS  PubMed  Google Scholar 

  • Nagai M, Ijichi S, Hall WW, Osame M (1995) Differential effect of TGF-beta 1 on the in vitro activation of HTLV-I and the proliferative response of CD8+ T lymphocytes in patients with HTLV-I-associated myelopathy (HAM/TSP). Clin Immunol Immunopathol 77:324–331

    Article  CAS  PubMed  Google Scholar 

  • Nagai M, Kubota R, Greten TF, Schneck JP, Leist TP, Jacobson S (2001) Increased activated human T cell lymphotropic virus type I (HTLV-I) Tax11-19-specific memory and effector CD8+ cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis: correlation with HTLV-I provirus load. J Infect Dis 183:197–205

    Article  CAS  PubMed  Google Scholar 

  • Nagai M, Yamano Y, Brennan MB, Mora CA, Jacobson S (2001) Increased HTLV-I proviral load and preferential expansion of HTLV-I Tax-specific CD8+ T cells in cerebrospinal fluid from patients with HAM/TSP. Ann Neurol 50:807–812

    Article  CAS  PubMed  Google Scholar 

  • Nakanishi K (2018) Unique Action of Interleukin-18 on T Cells and Other Immune Cells. Front Immunol 9:763

    Article  PubMed  PubMed Central  Google Scholar 

  • Pinto MT, Malta TM, Rodrigues ES, Pinheiro DG, Panepucci RA, Malmegrim de Farias KC, Sousa Ade P, Takayanagui OM, Tanaka Y, Covas DT, Kashima S (2014) Genes related to antiviral activity, cell migration, and lysis are differentially expressed in CD4(+) T cells in human t cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis patients. AIDS Res Hum Retroviruses 30:610–622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC (1980) Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A 77:7415–7419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rafatpanah H, Farid Hosseini R, Pourseyed SH (2013) The impact of immune response on HTLV-I in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Iran J Basic Med Sci 16:235–241

    PubMed  PubMed Central  Google Scholar 

  • Rk G, Ms K, Kk G, Kurapati M, M S, T MA, P C, G SR, S N, P K, K SS, H SR (2015) Evaluation of Hs-CRP levels and interleukin 18 (-137G/C) promoter polymorphism in risk prediction of coronary artery disease in first degree relatives. PLoS One 10:e0120359

    Article  Google Scholar 

  • Rocha-Junior MC, Haddad R, Ciliao Alves DC, de Deus Wagatsuma VM, Mendes-Junior CT, Deghaide NH, Takayanagui OM, Covas DT, Donadi EA, Kashima S (2012) Interleukin-18 and interferon-gamma polymorphisms are implicated on proviral load and susceptibility to human T-lymphotropic virus type 1 infection. Tissue Antigens 80:143–150

    Article  CAS  PubMed  Google Scholar 

  • Rosado J, Morales S, Lopez G, Clark D, Verdonck K, Gotuzzo E, Van Camp G, Talledo M (2017) The FAS-670 AA genotype is associated with high proviral load in peruvian HAM/TSP patients. J Med Virol 89:726–731

    Article  CAS  PubMed  Google Scholar 

  • Saito M, Jain P, Tsukasaki K, Bangham CR (2012) HTLV-1 infection and its associated diseases. Leuk Res Treatment 2012:123637

    PubMed  PubMed Central  Google Scholar 

  • Salehi M, Shokouhi Mostafavi SK, Ghasemian A, Gholami M, Kazemi-Vardanjani A, Rahimi MK (2017) Seroepidemiology of HTLV-1 and HTLV-2 Infection in Neyshabur City, North-Eastern Iran, during 2010–2014. Iran Biomed J 21:57–60

    Article  PubMed  PubMed Central  Google Scholar 

  • Sato T, Coler-Reilly A, Utsunomiya A, Araya N, Yagishita N, Ando H, Yamauchi J, Inoue E, Ueno T, Hasegawa Y, Nishioka K, Nakajima T, Jacobson S, Izumo S, Yamano Y (2013) CSF CXCL10, CXCL9, and neopterin as candidate prognostic biomarkers for HTLV-1-associated myelopathy/tropical spastic paraparesis. PLoS Negl Trop Dis 7:e2479

    Article  PubMed  PubMed Central  Google Scholar 

  • Satou Y, Utsunomiya A, Tanabe J, Nakagawa M, Nosaka K, Matsuoka M (2012) HTLV-1 modulates the frequency and phenotype of FoxP3+CD4+ T cells in virus-infected individuals. Retrovirology 9:46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shoeibi A, Etemadi M, Moghaddam Ahmadi A, Amini M, Boostani R (2013) “HTLV-I infection” twenty-year research in Neurology Department of Mashhad University of Medical Sciences. Iran J Basic Med Sci 16:202–207

    PubMed  PubMed Central  Google Scholar 

  • Tokunaga R, Zhang W, Naseem M, Puccini A, Berger MD, Soni S, McSkane M, Baba H, Lenz HJ (2018) CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation—a target for novel cancer therapy. Cancer Treat Rev 63:40–47

    Article  CAS  PubMed  Google Scholar 

  • Trevino A, Lopez M, Vispo E, Aguilera A, Ramos JM, Benito R, Roc L, Eiros JM, de Mendoza C, Soriano V, Group HSS (2012) Development of tropical spastic paraparesis in human T-lymphotropic virus type 1 carriers is influenced by interleukin 28B gene polymorphisms. Clin Infect Dis 55:e1-4

    Article  Google Scholar 

  • Vallinoto AC, Santana BB, dos Santos EL, Santo RR, Hermes RB, Sousa RC, Cayres-Vallinoto I, Machado LF, Ishak MO, Ishak R (2012) FAS-670A/G single nucleotide polymorphism may be associated with human T lymphotropic virus-1 infection and clinical evolution to TSP/HAM. Virus Res 163:178–182

    Article  CAS  PubMed  Google Scholar 

  • Vallinoto AC, Santana BB, Sa KS, Ferreira TC, Sousa RC, Azevedo VN, Feitosa RN, Machado LF, Ishak MO, Ishak R (2015) HTLV-1-associated myelopathy/tropical spastic paraparesis is not associated with SNP rs12979860 of the IL-28B gene. Mediators Inflamm 2015:804167

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang F, Lu Z, Hawkes M, Yang H, Kain KC, Liles WC (2010) Fas (CD95) induces rapid, TLR4/IRAK4-dependent release of pro-inflammatory HMGB1 from macrophages. J Inflamm (Lond) 7:30

    Article  Google Scholar 

  • Wawrusiewicz-Kurylonek N, Chorazy M, Posmyk R, Zajkowska O, Zajkowska A, Kretowski AJ, Tarasiuk J, Kochanowicz J, Kulakowska A (2018) The FOXP3 rs3761547 gene polymorphism in multiple sclerosis as a male-specific risk factor. Neuromolecular Med 20:537–543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson N, Driss A, Solomon W, Dickinson-Copeland C, Salifu H, Jain V, Singh N, Stiles J (2013) CXCL10 gene promoter polymorphism -1447A>G correlates with plasma CXCL10 levels and is associated with male susceptibility to cerebral malaria. PLoS ONE 8:e81329

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu Z, You Z, Zhang C, Li Z, Su X, Zhang X, Li Y (2012) Association between functional polymorphisms of Foxp3 gene and the occurrence of unexplained recurrent spontaneous abortion in a Chinese Han population. Clin Dev Immunol 2012:896458

    Article  PubMed  Google Scholar 

  • Yamamoto-Taguchi N, Satou Y, Miyazato P, Ohshima K, Nakagawa M, Katagiri K, Kinashi T, Matsuoka M (2013) HTLV-1 bZIP factor induces inflammation through labile Foxp3 expression. PLoS Pathog 9:e1003630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamano Y, Coler-Reilly A (2017) HTLV-1 induces a Th1-like state in CD4(+)CCR4(+) T cells that produces an inflammatory positive feedback loop via astrocytes in HAM/TSP. J Neuroimmunol 304:51–55

    Article  CAS  PubMed  Google Scholar 

  • Virgínia M D Wagatsuma DCC-A, Maurício C Rocha–Junior, Rodrigo Haddad, Oswaldo M Takayanagui, Eduardo A Donadi, Dimas T Covas, Simone Kashima (2011) Association of interleukin - 18 gene polymorphism with susceptibility or protective effect to HTLV-1 infection. Retrovirology.

Download references

Acknowledgments

We acknowledged all patients with HAM-TSP, HTLV-1 carriers, and healthy blood donors for their contribution in the current study.

Funding

The present study was financially supported by Mashhad University of Medical Sciences, Mashhad, Iran, and Kerman University of Medical Sciences, Kerman, Iran.

Author information

Authors and Affiliations

Authors

Contributions

Houshang Rafatpanah gave the blood samples and information regarding demographic data of patients with HAM/TSP and HTLV-1 carriers. He also read the manuscript; Zohreh Poursina helped to do DNA extraction from samples of patients with HAM-TSP and HTLV-1 carriers and read the manuscript; Hadi Zare Marzouni helped for DNA extraction from samples of healthy blood donors and performed PCR for all polymorphisms. He also helped for writing of the manuscript and data analysis; Reza Boostani affirmed the diagnosis of HAM/TSP and introduced the patients to participate in our study; Mahdi Atabaki helped for writing of the manuscript; Reza Farid-Hosseini gave the consultation and read the manuscript; Jalil Tavakkol-Afshari read the manuscript and helped with the laboratory facilities for molecular techniques; Mojgan Mohammadi designed the study, supervised and financially supported the project, and wrote the manuscript.

Corresponding author

Correspondence to Mojgan Mohammadi.

Ethics declarations

Competing interests

The authors declare that they have no conflict of interest.

Ethics approval

This study approved by the Ethics Committee of Mashhad University of Medical sciences and the code was 931203.

Consent for publication

All authors of the manuscript have read and agreed to its content and are accountable for all aspects of the accuracy and integrity of the manuscript in accordance with ICMJE criteria. All authors agreed to the terms of the BioMed Central Copyright and License Agreement. All authors approved that the current article is original and has not already been published in another journal, and is not currently under consideration by a journal.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rafatpanah, H., Poursina, Z., Boostani, R. et al. A significant association between CXCL10 -1447 A > G and IL18 -607 C > A gene polymorphism with human T-cell lymphotropic virus type 1 associated myelopathy/tropical spastic paraparesis (HAM-TSP), a case-control report from city of Mashhad, Iran. J. Neurovirol. 27, 249–259 (2021). https://doi.org/10.1007/s13365-021-00946-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-021-00946-4

Keywords

Navigation