Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: High proviral load strongly predisposes to HAM/TSP

Nagai, Masahiro; Usuku, Koichiro; Matsumoto, Wataru; Kodama, Daisuke; Takenouchi, Norihiro; Moritoyo, Takashi; Hashiguchi, Seiichi; Ichinose, Mamoru; Bangham, R. M.; Izumo, Shuji; Osame, Mitsuhiro

doi:10.1097/00042560-199904010-00238

Cited by 166 publications

(281 citation statements)

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“…This is supported by our observation that PC-sIL-6R protein was detected at higher levels in sera of HAM/TSP patients (Fig. 4b) in which Tax-positive cells were present in peripheral blood 43 compared with sera of healthy people or ATL patients, who are known to barely contain them. These results indicate that Tax enhances production of PCsIL-6R in HTLV-I-infected T cells.…”

Section: Discussionsupporting

confidence: 79%

Human T‐cell leukemia virus type‐I Tax induces expression of interleukin‐6 receptor (IL‐6R): Shedding of soluble IL‐6R and activation of STAT3 signaling

Horiuchi

Yamamoto

Dewan

et al. 2006

Intl Journal of Cancer

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Human T‐cell leukemia virus type‐I (HTLV‐I) encodes for the viral protein Tax, which is known to significantly disrupt transcriptional control of cytokines, cytokine receptors and other immuno‐modulatory proteins in T cells. Specific dysregulation of these factors can alter the course and pathogenesis of infection. Soluble interleukin‐6 receptor (sIL‐6R) was shown to circulate at elevated levels in HTLV‐I‐infected patients, and high expressions of IL‐6R and sIL‐6R by HTLV‐I‐infected T cells were clinically and experimentally associated with Tax activity. To examine roles of Tax in expression of the IL‐6R gene, the JPX‐9 cell line was used, which is derived from Jurkat cell line expressing Tax cDNA. Over‐expression of Tax enhanced IL‐6R expression but not in Tax mutant JPX‐9/M cell line. The clinical relevance of these observations was further demonstrated by ELISA using sera obtained from HTLV‐I‐infected patients. Our results revealed that sIL‐6R levels were apparently elevated in HAM/TSP patients who were expressing Tax in their cells, while ATL patients' cells barely expressed Tax. HTLV‐I‐infected T‐cell lines stimulated by IL‐6/sIL‐6R showed gp130‐mediated STAT3 activity. IL‐6/sIL‐6R enhanced proliferation of HTLV‐I‐infected T cells in association with activation of STAT3. Consequently, Tax‐mediated regulations of IL‐6R and sIL‐6R observed in HTLV‐I‐associated disorders may contribute to proliferation of HTLV‐I‐infected T cells through activation of inducible STAT3, and ultimately affect malignant growth and transformation of T cells by HTLV‐I. © 2006 Wiley‐Liss, Inc.

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Section: Discussionsupporting

confidence: 79%

Human T‐cell leukemia virus type‐I Tax induces expression of interleukin‐6 receptor (IL‐6R): Shedding of soluble IL‐6R and activation of STAT3 signaling

Horiuchi

Yamamoto

Dewan

et al. 2006

Intl Journal of Cancer

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“…A patient with HAM/TSP develops a progressive spastic weakness of the legs, often accompanied by low back pain and urinary frequency or urgency (Gessain & Gout 1992;Nakagawa et al 1995). The disease typically progresses for several months, leaving the patient bedbound, chair-bound, or walking with sticks.…”

Section: Ham/tsp and Other Chronic Inflammatory Diseases Associated Wmentioning

confidence: 99%

“…females is 1:2. The peak age at onset of HAM/TSP is in the 40s, but the disease can present at almost any age; it is rare in children (Nakagawa et al 1995).…”

Section: Ham/tsp and Other Chronic Inflammatory Diseases Associated Wmentioning

confidence: 99%

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Genetic control and dynamics of the cellular immune response to the human T–cell leukaemia virus, HTLV–I

Bangham

Hall

Jeffery

et al. 1999

Phil. Trans. R. Soc. Lond. B

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About 1% of people infected with the human T-cell leukaemia virus, type 1 (HTLV-I) develop a disabling chronic in£ammatory disease of the central nervous system known as HTLV-I-associated myelopathy/ tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have a vigorous immune response to HTLV-I, and it has been widely suggested that this immune response, particularly the HTLV-I-speci¢c cytotoxic T-lymphocyte (CTL) response, causes the tissue damage that is seen in HAM/TSP. In this paper we summarize recent evidence that a strong CTL response to HTLV-I does in fact protect against HAM/TSP by reducing the proviral load of HTLV-I. We conclude that HTLV-I is persistently replicating at a high level, despite the relative constancy of its genome sequence. These results imply that antiretroviral drugs could reduce the risk of HAM/TSP by reducing the viral load, and that an e¡ective anti-HTLV-I vaccine should elicit a strong CTL response to the virus. The dynamic nature of the infection also has implications for the epidemiology and the evolution of HTLV-I.

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“…A chronic in£ammatory disease of the central nervous system, namely HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), is strongly associated with a high HTLV-1 proviral load (Nagai et al 1998). We have observed a signi¢cant positive correlation in healthy HTLV-1 carriers between the proviral load of HTLV-1 and the frequency of CTLs speci¢c to an immunodominant A * 02-restricted epitope in Tax, Tax11-19, as measured with £uorescent-labelled tetrameric complexes of HLA-A * 02/b-2 microglobulin/Tax 11-19 peptide (¢gure 1a).…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic T–cell abundance and virus load in human immunodeficiency virus type 1 and human T–cell leukaemia virus type 1

Wodarz

Hall

Usuku

et al. 2001

Proc. R. Soc. Lond. B

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The correlation between virus load and speci¢c cytotoxic T-lymphocyte (CTL) frequency during the chronic phase in human immunode¢ciency virus type 1 (HIV-1) infection has been found to be negative in cross-sectional studies. We report here that, in infection with the related retrovirus human T-cell leukaemia virus type 1 (HTLV-1), the correlation is positive in asymptomatic carriers and zero in patients with the associated in£ammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We demonstrate that the direction of the correlation may depend on the e¤cacy of the CTL response using mathematical models. We conclude that the CTL response is e¡ective in asymptomatic carriers of HTLV-1, but ine¡ective in patients with HAM/TSP. Virus-mediated impairment of speci¢c CTL production in HIV-1 infection can account for the negative correlation observed.

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Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: High proviral load strongly predisposes to HAM/TSP

Cited by 166 publications

References 0 publications

Human T‐cell leukemia virus type‐I Tax induces expression of interleukin‐6 receptor (IL‐6R): Shedding of soluble IL‐6R and activation of STAT3 signaling

Human T‐cell leukemia virus type‐I Tax induces expression of interleukin‐6 receptor (IL‐6R): Shedding of soluble IL‐6R and activation of STAT3 signaling

Genetic control and dynamics of the cellular immune response to the human T–cell leukaemia virus, HTLV–I

Cytotoxic T–cell abundance and virus load in human immunodeficiency virus type 1 and human T–cell leukaemia virus type 1

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