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      Comparison of HTLV-I Proviral Load in Adult T Cell Leukemia/Lymphoma (ATL), HTLV-I-Associated Myelopathy (HAM-TSP) and Healthy Carriers

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          Abstract

          Objective(s): Human T Lymphocyte Virus Type one (HTLV-I) is a retrovirus that infects about 10-20 million people worldwide. Khorasan province in Iran is an endemic area. The majority of HTLV-I-infected individuals sustain healthy carriers but small proportion of infected population developed two progressive diseases: HAM/TSP and ATL. The proviral load could be a virological marker for disease monitoring, therefore in the present study HTLV-I proviral load has been evaluated in ATL and compared to HAM/TSP and healthy carriers.

          Materials and Methods: In this case series study, 47 HTLV-I infected individuals including 13 ATL, 23 HAM/TSP and 11 asymptomatic subjects were studied. Peripheral blood mononuclear cells (PBMCs) were investigated for presence of HTLV-I DNA provirus by PCR using LTR and Tax fragments. Then in infected subjects, HTLV-I proviral load was measured using real time PCR TaqMan method.

          Results: The average age of patients in ATL was 52±8, in HAM/TSP 45.52±15.17 and in carrier’s 38.65±14.9 years which differences were not statistically significant. The analysis of data showed a significant difference in mean WBC among study groups (ATL vs HAM/TSP and carriers P=0.0001). Moreover, mean HTLV-I proviral load was 11967.2 ± 5078, 409 ± 71.3 and 373.6 ± 143.3 in ATL, HAM/TSP and Healthy Carriers, respectively. The highest HTLV-I proviral load was measured in ATL group that had a significant correlation with WBC count (R=0.495, P=0.001). The proviral load variations between study groups was strongly significant (ATL vs carrier P=0.0001; ATL vs HAM/TSP P= 0.0001 and HAM/TSP vs carriers P< 0.05).

          Conclusion : The present study demonstrated that HTLV-I proviral load was higher in ATL group in comparison with HAM/TSP and healthy carriers. Therefore, HTLV-I proviral load is a prognostic factor for development of HTLV-I associated diseases and can be used as a monitoring marker for the efficiency of therapeutic regime.

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          HTLV Tax: A Fascinating Multifunctional Co-Regulator of Viral and Cellular Pathways

          Robert Currer, Rachel Van Duyne, Elizabeth Jaworski … (2012)
          Human T-cell lymphotropic virus type 1 (HTLV-1) has been identified as the causative agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus infects between 15 and 20 million people worldwide of which approximately 2–5% develop ATL. The past 35 years of research have yielded significant insight into the pathogenesis of HTLV-1, including the molecular characterization of Tax, the viral transactivator, and oncoprotein. In spite of these efforts, the mechanisms of oncogenesis of this pleiotropic protein remain to be fully elucidated. In this review, we illustrate the multiple oncogenic roles of Tax by summarizing a recent body of literature that refines our understanding of cellular transformation. A focused range of topics are discussed in this review including Tax-mediated regulation of the viral promoter and other cellular pathways, particularly the connection of the NF-κB pathway to both post-translational modifications (PTMs) of Tax and subcellular localization. Specifically, recent research on polyubiquitination of Tax as it relates to the activation of the IkappaB kinase (IKK) complex is highlighted. Regulation of the cell cycle and DNA damage responses due to Tax are also discussed, including Tax interaction with minichromosome maintenance proteins and the role of Tax in chromatin remodeling. The recent identification of HTLV-3 has amplified the importance of the characterization of emerging viral pathogens. The challenge of the molecular determination of pathogenicity and malignant disease of this virus lies in the comparison of the viral transactivators of HTLV-1, -2, and -3 in terms of transformation and immortalization. Consequently, differences between the three proteins are currently being studied to determine what factors are required for the differences in tumorogenesis.
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            High prevalence of HTLV-I infection in Mashhad, Northeast Iran: a population-based seroepidemiology survey.

            Houshang Rafatpanah, Farhad Fathimoghadam, Reza Farid … (2011)
            Mashhad, in the northeast of Iran has been suggested as an endemic area for human T cell lymphotropic virus type I (HTLV-I) infection since 1996. We performed a community-based seroepidemiology study to examine the prevalence and risk factors for HTLV-I infection in the city of Mashhad. Between May and September 2009, overall 1678 subjects from all the 12 geographical area of Mashhad were selected randomly by multistage cluster sampling for HTLV antibody. The study population included 763 males and 915 females, with the mean age of 29.1 ± 18.5 years. 1654 serum samples were assessed for HTLV antibody using ELISA and reactive samples were confirmed by Western blot and PCR. The overall prevalence of HTLV-I infection in whole population was 2.12% (95% CI, 1.48-2.93) with no significant difference between males and females (p = 0.093) and the prevalence of HTLV-II seropositivity was 0.12% (95% CI, 0.02-0.44). The HTLV-I Infection was associated with age (p<0.001), marital status (p<0.001), education (p = 0.047), and history of blood transfusion (p = 0.009), surgery (p<0.001), traditional cupping (p = 0.002), and hospitalization (p = 0.004). In logistic regression analysis, age was the only variable that had a significant relation with the infection (p = 0.006, OR = 4.33). Our results demonstrated that Mashhad still remains an endemic area for HTLV-I infection despite routine blood screening. Thus, further strategies are needed for prevention of the virus transmission in whole population. Copyright © 2011 Elsevier B.V. All rights reserved.
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              Clinical Pathophysiology of Human T-Lymphotropic Virus-Type 1-Associated Myelopathy/Tropical Spastic Paraparesis

              Yoshihisa Yamano, Tomoo Sato (2012)
              Human T-lymphotropic virus type 1 (HTLV-1), a human retrovirus, is the causative agent of a progressive neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic inflammatory disease of the central nervous system and is characterized by unremitting myelopathic symptoms such as spastic paraparesis, lower limb sensory disturbance, and bladder/bowel dysfunction. Approximately 0.25–3.8% of HTLV-1-infected individuals develop HAM/TSP, which is more common in women than in men. Since the discovery of HAM/TSP, significant advances have been made with respect to elucidating the virological, molecular, and immunopathological mechanisms underlying this disease. These findings suggest that spinal cord invasion by HTLV-1-infected T cells triggers a strong virus-specific immune response and increases proinflammatory cytokine and chemokine production, leading to chronic lymphocytic inflammation and tissue damage in spinal cord lesions. However, little progress has been made in the development of an optimal treatment for HAM/TSP, more specifically in the identification of biomarkers for predicting disease progression and of molecular targets for novel therapeutic strategies targeting the underlying pathological mechanisms. This review summarizes current clinical and pathophysiological knowledge on HAM/TSP and discusses future focus areas for research on this disease.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Iran J Basic Med Sci
                Journal ID (iso-abbrev): Iran J Basic Med Sci
                Journal ID (publisher-id): IJBMS
                Title: Iranian Journal of Basic Medical Sciences
                Publisher: Mashhad University of Medical Sciences (Mashhad, Iran )
                ISSN (Print): 2008-3866
                ISSN (Electronic): 2008-3874
                Publication date (Print): March 2013
                Volume: 16
                Issue: 3
                Pages: 208-212
                Affiliations
                [1 ]Inflammation and inflammatory research centre, Medical School, Mashhad University of Medical Science, Mashhad- Iran
                [2 ]Internal medicine Dept. Medical School, Mashhad University of Medical Science, Mashhad- Iran
                [3 ]Internal Medicine Dept, Amir al Moemenin Hospital, Arak University of Medical Sciences.
                [4 ]Navid Medical Lab, Mashhad- Iran
                Author notes
                [* ]Corresponding author: Abass Shirdel, Inflammation and inflammatory research centre and internal medicine, Medical School, Mashhad University of Medical Science, Mashhad- Iran; E-mail: Shirdela@mums.ac.ir
                Article
                Publisher ID: ijbms-16-208
                PMC ID: 3881246
                SO-VID: 95a105cb-22b2-4a67-9856-555625923545
                Copyright © © 2013: Iranian Journal of Basic Medical Sciences
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 11 August 2012
                Date accepted : 18 February 2013
                Categories
                Subject: Original Article

                Keywords: htlv-i,ham/tsp,atl,htlv-i proviral load
                Data availability:
                Keywords: htlv-i, ham/tsp, atl, htlv-i proviral load

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