Evolution of HTLV-1 proviral load in patients from Salvador, Brazil

Olavarria, Viviana Nilla; Gomes, Alline do Nascimento; Kruschewsky, Ramon de Almeida; Galvão–Castro, Bernardo; Grassi, Maria Fernanda Rios

doi:10.1016/j.bjid.2012.06.022

Cited by 10 publications

(5 citation statements)

References 24 publications

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“…It is generally reported that high HTLV‐1 proviral load is a risk factor for HAM/TSP (ie, higher PVL in HAM/TSP patients than in ACs), yet in this study there was no correlation between HTLV‐1 PVL and the degree of spinal cord atrophy. This result is consistent with previous findings that HTLV‐1 PVL remains stable despite the progression of disability in most HAM/TSP cases and suggests that disability progression is due to neurodegeneration and irreversible tissue loss . Thus, antiviral therapies that reduce PVL might not be sufficient to arrest disability progression.…”

Section: Discussionsupporting

confidence: 92%

“…This result is consistent with previous findings that HTLV-1 PVL remains stable despite the progression of disability in most HAM/TSP cases and suggests that disability progression is due to neurodegeneration and irreversible tissue loss. 31 Thus, antiviral therapies that reduce PVL might not be sufficient to arrest disability progression. This study did not assess whether PVL or other inflammatory markers in the cerebrospinal fluid may be a better correlate of HAM/TSP spinal cord atrophy.…”

Section: Discussionmentioning

confidence: 99%

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In vivo imaging of spinal cord atrophy in neuroinflammatory diseases

Liu

Nair

Vuolo

et al. 2014

Annals of Neurology

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Objective Spinal cord atrophy is prominent in chronic progressive neurologic diseases such as Human-T-cell lymphotropic virus type-1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). Here we compared the spinal cord cross-sectional area (SCCSA) in HAM/TSP and MS to that of healthy volunteers (HV). Methods SCCSA and clinical disability scores were measured in 18 HAM/TSP, 4 asymptomatic carriers (AC) of HTLV-1, 18 MS, and 10 HV from a 3T MRI. SCCSA measured in patients and AC were compared to that of HV and correlated with disability scores. Results The entire spinal cord in HAM/TSP was thin compared to HV, whereas only the cervical cord in MS was thinner than HV (p<0·0001). In HAM/TSP, SCCSA extensively correlated with Ambulation Index, whereas only the cervical cord correlated with disease duration (p<0·05). In MS, the SCCSA extensively correlated with Scripps Neurologic Rating Score and the Expanded Disability Status Scale (p<0·05). One of the four ACs showed atrophy in a pattern similar to HAM/TSP. Interpretation These results are in accordance with the findings that whereas over half of all lesions in an MS cord are seen in the upper cervical cord, most of the pathology in HAM/TSP is seen in the thoracolumbar cord, which in turn may be responsible for more extensive cord atrophy seen in HAM/TSP. Imaging marker such as SCCSA might serve as a surrogate endpoint in clinical trials, especially to assess the neuroprotective impact of various therapies.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

In vivo imaging of spinal cord atrophy in neuroinflammatory diseases

Liu

Nair

Vuolo

et al. 2014

Annals of Neurology

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“…This correlates with other studies that have shown axonal loss and demyelination as clinical manifestations of HAM/TSP seen on histopathology (Liu et al 2014). In this study the data from the hu-mice has also corroborated previous findings that have reported stable PVL despite disease progression due to neurodegeneration (Liu et al 2014; Olavarria et al 2012). Thus far, both the mouse models show comparable level of infection and neuropathogenesis.…”

Section: Discussionsupporting

confidence: 90%

HTLV-1 Infection and Neuropathogenesis in the Context of Rag1-/-γc-/- (RAG1-Hu) and BLT Mice

Ginwala

Caruso

Khan

et al. 2017

J Neuroimmune Pharmacol

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To date, the lack of a suitable small animal model has hindered our understanding of Human T-cell lymphotropic virus (HTLV)-1 chronic infection and associated neuropathogenesis defined as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The host immune response plays a critical role in the outcome of HTLV-1 infection, which could be better tested in the context of humanized (hu) mice. Thus, we employ here the Balb/c-Rag1−/−γc−/− or Rag1 as well as Bone marrow-Liver-Thymic (BLT) mouse models for engraftment of human CD34+ hematopoietic stem cells. Flow cytometry and histological analyses confirmed reconstitution of Rag1 and BLT mice with human immune cells. Following HTLV-1 infection, proviral load (PVL) was detected in the blood of Rag-1 and BLT hu-mice as early as 2 weeks post-infection (wpi) with sustained elevation in the subsequent weeks followed by Tax expression. Additionally, infection was compared between adult and neonatal Rag1 mice with both PVL and Tax expression considerably higher in the adult Rag1 mice as compared to the neonates. Establishment of peripheral infection led to lymphocytic infiltration with concomitant Tax expression and resulting myelin disruption within the central nervous system of infected mice. In addition, up-regulation in the expression of several immune checkpoint mediators such as programmed cell death-1 (PD-1), T-cell Ig and ITIM domain (TIGIT), and T cell Ig and mucin domain-3 protein (Tim-3) were observed on CD8+ T cells in various organs including the CNS of infected hu-mice. Collectively, these studies represent the first attempt to establish HTLV-1 neuropathogenesis in the context of Rag-1 and BLT hu-mice as potential novel tools for understanding HTLV-1 neuropathogenesis and testing of novel therapies such as immune checkpoint blockade in the amelioration of chronic HTLV-1 infection.

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“…Meanwhile, PVL is an important biological indicator of HTLV‐1 pathogenesis and can tell us whether the virus is correlated with the clinical manifestation of the disease [Lins et al, ]. However, high PVL is a risk factor for HAM/TSP, and there is an overlap for levels of PVL in peripheral blood between ACs and HAM/TSP patients [Olavarria et al, ]. Therefore, HTLV‐1 PVL alone, in virus‐infected subjects, cannot be a good prognostic factor for disease occurrence.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of HTLV‐1 HBZ and proviral load, together with host IFN λ3, in pathogenesis of HAM/TSP

Mozhgani

Jaberi

Rezaee

et al. 2016

Journal of Medical Virology

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Human T-cell lymphotropic virus 1 (HTLV-1) is associated with two progressive diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Although HTLV-1 proviral load (PVL) has been introduced as a risk factor for these diseases' progression, it is not sufficient on its own to yield an accurate estimation of the outcome of the infection. In the present study, PVL and HTLV-1 basic leucine zipper factor (HBZ) expression level as viral factors, and IFN λ3 as a host factor, were evaluated in HAM/TSP patients and HTLV-1 asymptomatic carriers (ACs). During 2014-2015, 12 HAM/TSP patients and 18 ACs who had been referred to the HTLV-1 Clinic, Ghaem Hospital, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran, were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated and the DNA and mRNA were extracted for quantification of HBZ, IFN λ3 expression, and PVL using real-time PCR (TaqMan method). Although the PVL was higher in the HAM/TSP group, with a 94% confidence interval, there were no considerable differences in terms of HBZ mRNA and PVL between ACs and HAM patients. IFN λ3 expression in the HAM/TSP group was significantly higher than in the ACs (P = 0.02). To the best of our knowledge, no study has evaluated the expression level of IFN λ3 in HTLV-1 positive patients. The immune response against HTLV-1 viral antigens and virulent factors will therefore further refine our knowledge of interactions between the virus and host in the pathogenesis of HTLV-1-related disorders. The virus PVL and the host IFN λ3 can be used as pathogenic factors of HTLV-1 infected patients at risk of HAM/TSP manifestation. J. Med. Virol. 89:1102-1107, 2017. © 2016 Wiley Periodicals, Inc.

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Evolution of HTLV-1 proviral load in patients from Salvador, Brazil

Cited by 10 publications

References 24 publications

In vivo imaging of spinal cord atrophy in neuroinflammatory diseases

In vivo imaging of spinal cord atrophy in neuroinflammatory diseases

HTLV-1 Infection and Neuropathogenesis in the Context of Rag1-/-γc-/- (RAG1-Hu) and BLT Mice

Evaluation of HTLV‐1 HBZ and proviral load, together with host IFN λ3, in pathogenesis of HAM/TSP

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