High production of RANTES and MIP-1α in the tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM)

Montanheiro, Patrícia; Vergara, María Paulina Posada; Smid, Jerusa; Duarte, Alberto José da Silva; Oliveira, Augusto César Penalva de; Casseb, Jorge

doi:10.1016/j.jneuroim.2007.05.015

Cited by 19 publications

(17 citation statements)

References 25 publications

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“…Previously, it has been reported that serum levels of MCP-1 are diminished in infected patients (93). However, enhanced levels of RANTES production and secretion have been documented in adult T-cell leukemia cell lines and PBMCs collected from HAM/TSP patients (94,95). Although it appears that exosomes do not contribute to the increased abundance of RANTES during HTLV-1 infection, it is possible that HTLV-1 infection or Tax expression could influence the production and secretion of other proinflammatory cytokines, including IL-6, via exosomes.…”

Section: C81 Mt2 and Ed(ϫ) Cell Lines Contain Inflammatorymentioning

confidence: 99%

Human T-lymphotropic Virus Type 1-infected Cells Secrete Exosomes That Contain Tax Protein

Jaworski

Narayanan

Duyne

et al. 2014

Journal of Biological Chemistry

134

170

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Background: Extracellular exosomes contain various functional elements. Results: Exosomal Tax protein causes phenotypic changes in uninfected cells. Conclusion: Exosomes may play critical roles in extracellular delivery of oncogenic material derived from HTLV-1-infected cells. Significance: Exosomal delivery of Tax and other putative oncogenic components produced during HTLV-1 infection potentially contributes to pathogenesis of adult T-cell leukemia, myelopathy, or tropical spastic paraparesis.

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Section: C81 Mt2 and Ed(ϫ) Cell Lines Contain Inflammatorymentioning

confidence: 99%

Human T-lymphotropic Virus Type 1-infected Cells Secrete Exosomes That Contain Tax Protein

Jaworski

Narayanan

Duyne

et al. 2014

Journal of Biological Chemistry

134

170

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“…A few studies have looked for a possible association between Il28B polymorphisms – rs8099917 and rs12979860 and HAM/TSP outcome, while examining the HTLV-1 proviral load as a confounder; those who did have reported controversial results [17] [9], [18]. The major finding of this study, so far, was the independent association of IL28B polymorphism SNP rs8099917 (GG) with the development of HAM/TSP when compared to asymptomatic HTLV-1 carriers.…”

Section: Discussionmentioning

confidence: 77%

“…In fact, PVL is important in HAM/TSP patients since they may have up to 5–6 times more HTLV-1 proviral DNA in PBMC when compared to asymptomatic carriers, what may be related to many of the immunologic responses discussed above [22]. Other genetic background characteristics, such as some HLA haplotypes, have been described as involved in HAM/TSP pathogenesis [23] or pro-inflammatory factors [17]. In this regard, IL28B polymorphisms are influenced by genetic ancestry.…”

Section: Discussionmentioning

confidence: 99%

IL28B Gene Polymorphism SNP rs8099917 Genotype GG Is Associated with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in HTLV-1 Carriers

et al. 2014

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BackgroundThe polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP.MethodsThe study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System.ResultsA multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96–4.27) and in rs8099917 genotype GG (OR = 7.61; IC95% = 1.82–31.72).ConclusionSubjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.

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“…MIP-1α plays a beneficial role in wound repair (DiPietro et al, 1998), but its overproduction has been associated with neurodegenerative diseases in mice and humans (Balashov et al, 1999; Man et al, 2007; Montanheiro et al, 2007; Reale et al, 2009; Tripathy et al, 2007;Wu and Proia, 2004). In our model, we propose that MIP-1α recruits large numbers of macrophages/microglia to the brain and that the activated microglia not only release MIP-1α to recruit more microglia but also release other factors [e.g.…”

Section: Discussionmentioning

confidence: 99%

“…We further showed that the chemokine MIP-1α is elevated in both serum and brain tissues of rats infected with PVC-211 MuLV (Li et al, 2009). MIP-1α can act as a leukocyte chemoattractant (Mentan et al, 2002) and elevated levels of this chemokine play a role in a number of neurodegenerative diseases (Balashov et al, 1999; Man et al, 2007; Montanheiro et al, 2007; Reale et al, 2009; Tripathy et al, 2007;Wu and Proia, 2004). However, it is unclear whether MIP-1α, by virtue of its ability to attract macrophages/microglia, is directly involved in the neurodegeneration caused by PVC-211 MuLV.…”

Section: Introductionmentioning

confidence: 99%

Importance of macrophage inflammatory protein-1α and splenic macrophages in neurodegeneration induced by PVC-211 murine leukemia virus

Zhang

Cmarik

et al. 2011

Virology

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We recently reported that infection of rats with the neurodegenerative disease-causing retrovirus PVC-211 MuLV results in elevated levels of the chemokine MIP-1α followed by the accumulation of activated microglia in the brain. To investigate the importance of MIP-1α in recruitment of microglia to the brain, we treated rats with MIP-1α antibodies before and after PVC-211 MuLV infection. This caused a delay in the development of paralysis which was associated with a decrease in activated microglia without affecting virus expression. To determine the source of activated microglia, rats were splenectomized 4 days after virus infection. Splenectomized rats showed a delay in disease development that was associated with decreased numbers of activated microglia without affecting virus expression. Together, these results suggest that MIP-1α is directly involved in the neurodegeneration induced in rats by PVC-211 MuLV by recruiting macrophages/microglia from the periphery into regions of the brain that eventually become diseased.

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High production of RANTES and MIP-1α in the tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM)

Cited by 19 publications

References 25 publications

Human T-lymphotropic Virus Type 1-infected Cells Secrete Exosomes That Contain Tax Protein

Human T-lymphotropic Virus Type 1-infected Cells Secrete Exosomes That Contain Tax Protein

IL28B Gene Polymorphism SNP rs8099917 Genotype GG Is Associated with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in HTLV-1 Carriers

Importance of macrophage inflammatory protein-1α and splenic macrophages in neurodegeneration induced by PVC-211 murine leukemia virus

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