Lack of tax diversity for tropical spastic paraparesis/human T-cell lymphotropic virus type 1 (HTLV-I) associated myelopathy development in HTLV-I-infected subjects in São Paulo, Brazil

Casseb, Jorge; Fukumori, L. M. I.; Vergara, María Paulina Posada; Sanabani, S.S.; Marchiori, Paulo Eurípedes; Duarte, Alberto José da Silva; Oliveira, A. C. P.

doi:10.1590/s0074-02762006000300008

Cited by 10 publications

(9 citation statements)

References 17 publications

(18 reference statements)

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“…9,13,14 However, in this study we clearly demonstrated the limitations in applying tax RFLP for subgrouping HTLV-1a because of the variability in the nucleotide composition of this gene. Therefore, we do not recommend use of the tax RFLP approach with the purpose of subtyping HTLV-1a.…”

Section: Iñiguez Et Al 1128mentioning

confidence: 71%

“…In addition, two polymorphic substitutions, C7424T and T7891C, were highly prevalent in HTLV-1aA Argentinean isolates, as also reported in Brazilian strains. 13,14 One sample (ArJ11-5), which presented an HTLV-1aA RFLP profile, missed the first polymorphic site characteristic of tax A (Table 1). In 2 of 15 samples, with tax B RFLP profile, the uncut pattern was produced because of a C8344 Ǟ T substitution.…”

mentioning

confidence: 99%

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HTLV-1ataxGene and Long Terminal Repeat Sequences from Argentinean Strains Reveal Disagreement withtaxRestriction Fragment Length Polymorphism Subtyping

Iñiguez

Otsuki²,

Gastaldello³

et al. 2007

AIDS Research and Human Retroviruses

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Sequence and cluster analysis have shown two HTLV-1a tax gene subgroups, tax A and tax B, which are related to long terminal repeat (LTR) molecular subtypes. On the basis of subgroup-specific nucleotide substitutions, restriction fragment length polymorphism (RFLP) analysis of the tax gene for subtyping HTLV-1a isolates was proposed. In this study we genetically characterized the tax gene from 63 HTLV-1-positive Argentinean individuals, including 14 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis and 49 healthy HTLV-1 carriers. RFLP analysis showed that 48 samples yielded the tax A profile (76.19%) and that 15 samples contained the uncut tax B profile (23.81%). However, the LTR and tax sequence analysis revealed that in fact only 2 from the 15 samples belonged to the HTLV-1aB subgroup, presenting four tax B subgroup-specific nucleotide substitutions. The tax gene cluster analysis also confirmed that the majority of Argentinean strains belonged to the Transcontinental HTLV-1aA subgroup. These results indicate that the tax gene RFLP assay which has been proposed and used by some authors to screen HTLV-1a subgroups, is not a suitable tool to perform molecular epidemiological characterization of HTLV-1a populations.

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Section: Iñiguez Et Al 1128mentioning

confidence: 71%

mentioning

confidence: 99%

HTLV-1ataxGene and Long Terminal Repeat Sequences from Argentinean Strains Reveal Disagreement withtaxRestriction Fragment Length Polymorphism Subtyping

Iñiguez

Otsuki²,

Gastaldello³

et al. 2007

AIDS Research and Human Retroviruses

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“…Moreover, Tax is the immunodominant target antigen recognized by the CTL response [14]. This protein contributes to the development and progression of HTLV-1-associated diseases [15]. HBZ is a regulatory gene in the later stages of the infection, and suppresses the expression of Tax to escape from the specific CTLs [16].…”

Section: Introductionmentioning

confidence: 99%

Triple Therapy with Prednisolone, Pegylated Interferon and Sodium Valproate Improves Clinical Outcome and Reduces Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Load, Tax and HBZ mRNA Expression in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

et al. 2015

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Considering that there is no effective treatment for human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis, this study aimed to assess the impact of triple combination therapy-interferon-α, valproic acid, and prednisolone-on clinical outcomes, main HTLV-1 viral factors, and host anti-HTLV-1 antibody response. HTLV-1 proviral load (PVL), and HBZ and Tax mRNA expression levels were measured in peripheral blood mononuclear cells of 13 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis before and after treatment with 180 μg pegylated interferon once a week, 10-20 mg/kg/day sodium valproate, and 5 mg/day prednisolone for 25 weeks using a TaqMan real-time polymerase chain reaction assay. Furthermore, anti-HTLV-1 titer, Osame Motor Disability Score, Ashworth spasticity scale, and urinary symptoms (through standard questionnaire and clinical monitoring) were assessed in patients before and after the treatment. HTLV-1 PVL and HBZ expression significantly decreased after the treatment [PVL from 1443±282 to 660±137 copies/10 4 peripheral blood mononuclear cells (p= 0.01); and HBZ from 8.0±1.5 to 3.0±0.66 (p<0.01)]. Tax mRNA expression decreased after the treatment from 2.26± 0.45 to 1.44±0.64, but this reduction was not statistically significant (p=0.10). Furthermore, anti-HTLV-1 titer reduced dramatically after the treatment, from 3123±395 to 815±239 (p<0.01). Clinical signs and symptoms, according to Osame Motor Disability Score and Ashworth score, improved significantly (both p<0.01). Urinary symptoms and sensory disturbances with lower back pain were reduced, though not to a statistically significant degree. Although signs and symptoms of spasticity were improved, frequent urination and urinary incontinence were not significantly affected by the triple therapy. The results provide new insight into the complicated conditions underlying HTLV-1-associated diseases.

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“…These data are presented in Table 1 and confirm the molecular signature previously described in Brazilian sequences of HTLV-1. 10,12 Two of the nucleotide substitutions at positions C7982T and G8231A resulted in amino acid changes of A2661V and S2744N.…”

mentioning

confidence: 99%

Tax Gene Characterization of Human T-Lymphotropic Virus Type 1 Strains from Brazilian HIV-Coinfected Patients

Magri

Brígido²,

Rodrigues³

et al. 2012

AIDS Research and Human Retroviruses

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The tax gene of human T-lymphotropic virus type 1 (HTLV-1) diverges among isolates according to geographic regions and has been classified into two genotypes: taxA and taxB. In Brazil, taxA is the most prevalent genotype in symptomatic and asymptomatic carriers. Few studies have been conducted in HIV-infected patients. The present study characterized the tax gene (1059 bp) in 13 Brazilian HIV-1/HTLV-1-coinfected patients from the south and southeast regions. The results confirmed the transcontinental HTLV-1 subgroup A of the Cosmopolitan subtype and showed high nucleotide similarity both among Brazilian sequences and in relation to the ATK prototype (99.5% and 99.2%, respectively). Six nucleotide substitutions were highly conserved among isolates, ranging from 76.9% to 100%: C7401T, T7914C, C7920T, C7982T, G8231A, and A8367C. The presence of the Brazilian molecular signature of genotype taxA was confirmed in all of the isolates, and they clustered into two Latin American clusters, which confirms the double introduction of HTLV-1 in Brazil.

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Lack of tax diversity for tropical spastic paraparesis/human T-cell lymphotropic virus type 1 (HTLV-I) associated myelopathy development in HTLV-I-infected subjects in São Paulo, Brazil

Abstract: The product of human T-cell

Cited by 10 publications

References 17 publications

HTLV-1ataxGene and Long Terminal Repeat Sequences from Argentinean Strains Reveal Disagreement withtaxRestriction Fragment Length Polymorphism Subtyping

HTLV-1ataxGene and Long Terminal Repeat Sequences from Argentinean Strains Reveal Disagreement withtaxRestriction Fragment Length Polymorphism Subtyping

Triple Therapy with Prednisolone, Pegylated Interferon and Sodium Valproate Improves Clinical Outcome and Reduces Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Load, Tax and HBZ mRNA Expression in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

Tax Gene Characterization of Human T-Lymphotropic Virus Type 1 Strains from Brazilian HIV-Coinfected Patients

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