Detection of human T-lymphotropic virus type I p40<sup>tax</sup>protein in cerebrospinal fluid cells from patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis

Moritoyo, Takashi; Izumo, Shuji; Moritoyo, Hiroyoko; Tanaka, Yuetsu; Kiyomatsu, Yoshimasa; Nagai, Masahiro; Usuku, Koichiro; Sorimachi, Masaru; Osame, Mitsuhiro

doi:10.3109/13550289909015810

Cited by 62 publications

(45 citation statements)

References 14 publications

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“…Such impairment may persist and propagate via the secretion of soluble factors such as cytokines, chemokines, or metalloproteinases (14), and eventually alter the cell homeostasis. In the case of TSP/HAM this view is consistent with i) the presence in the lesions of cells expressing the viral product tax (8,15), which is known to transactivate many cellular genes including several inflammatory molecules (16); ii) the expression of inflammatory cytokines in infiltrated T cells and astrocytes, and iii) the expression pattern of metalloproteinases and their inhibitors (17).…”

Section: Introductionsupporting

confidence: 57%

Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy

García-Vallejo

Domínguez

Tamayo

2005

Braz J Med Biol Res

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Viruses share antigenic sites with normal host cell components, a phenomenon known as molecular mimicry. It has long been suggested that viral infections might trigger an autoimmune response by several mechanisms including molecular mimicry. More than 600 antiviral monoclonal antibodies generated against 11 different viruses have been reported to react with 3.5% of cells specific for uninfected mouse organs. The main pathological feature of tropical spastic paraparesis/ human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (TSP/HAM) is a chronic inflammation of the spinal cord characterized by perivascular cuffing of mononuclear cells accompanied by parenchymal lymphocytic infiltration. We detected the presence of autoantibodies against a 98-to 100-kDa protein of in vitro cultured human astrocytes and a 33-to 35-kDa protein from normal human brain in the serum of HTLV-I-seropositive individuals. The two cell proteins exhibited molecular mimicry with HTLV-I gag and tax proteins in TSP/HAM patients, respectively. Furthermore, the location of 33-to 35-kDa protein cross-reaction correlated with the anatomical spinal cord areas (in the rat model) in which axonal damage has been reported in several cases of TSP/HAM patients. Our experimental evidence strongly suggests that the demyelinating process occurring in TSP/ HAM may be mediated by molecular mimicry between domains of some viral proteins and normal cellular targets of the spinal cord sections involved in the neurodegeneration.

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Section: Introductionsupporting

confidence: 57%

Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy

García-Vallejo

Domínguez

Tamayo

2005

Braz J Med Biol Res

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“…Researchers have worked to characterize these cells over the years; together, their findings suggest that the infiltrates are dominated by CD4 + T cells with relatively high proviral loads and elevated Tax and IFN-γ expression (43)(44)(45). We hypothesized that a substantial portion of the infiltrate may be made up of infected CD4 Figure 4C).…”

Section: Discussionmentioning

confidence: 99%

HTLV-1 induces a Th1-like state in CD4+CCR4+ T cells

Araya¹,

Sato²,

Ando³

et al. 2014

J. Clin. Invest.

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“…After thorough PBS washes, sections were incubated with biotinylated donkey anti-goat IgG (Amersham Biosciences) at 1:1000 in PBS/0.3% Tx/1% NDS. After rinses, the signal was amplified with the tyramide signal amplification kit (PerkinElmer, Courtaboeuf, France) (Moritoyo et al, 1999;Qvigstad et al, 2002;El Meskini et al, 2005), followed by a fluorochrome Alexa 594-coupled streptavidin (Invitrogen, Eugene, OR). Sections were mounted onto gelatin-coated glass in Vectashield hardset mounting medium (Vector Laboratories) and coverslipped for light and fluorescence microscopic analysis.…”

Section: Methodsmentioning

confidence: 99%

Phenotype of Striatofugal Medium Spiny Neurons in Parkinsonian and Dyskinetic Nonhuman Primates: A Call for a Reappraisal of the Functional Organization of the Basal Ganglia

Nadjar¹,

Brotchie²,

Guigoni³

et al. 2006

J. Neurosci.

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The classic view of anatomofunctional organization of the basal ganglia is that striatopallidal neurons of the "indirect" pathway express D 2 dopamine receptors and corelease enkephalin with GABA, whereas striatopallidal neurons of the "direct" pathway bear D 1 dopamine receptors and corelease dynorphin and substance P with GABA. Although many studies have investigated the pathophysiology of the basal ganglia after dopamine denervation and subsequent chronic levodopa (L-dopa) treatment, none has ever considered the possibility of plastic changes leading to profound reorganization and/or biochemical phenotype modifications of medium spiny neurons. Therefore, we studied the phenotype of striatal neurons in four groups of nonhuman primates, including the following: normal, parkinsonian, parkinsonian chronically treated with L-dopa without exhibiting dyskinesia, and parkinsonian chronically treated with L-dopa exhibiting overt dyskinesia. To identify striatal cells projecting to external (indirect) or internal (direct) segments of the globus pallidus, the retrograde tracer cholera toxin subunit B (CTb) was injected stereotaxically into the terminal areas. Using immunohistochemistry techniques, brain sections were double labeled for CTb and dopamine receptors, opioid peptides, or the substance P receptor (NK1). We also used HPLC-RIA to assess opioid levels throughout structures of the basal ganglia. Our results suggest that medium spiny neurons retain their phenotype because no variations were observed in any experimental condition. Therefore, it appears unlikely that dyskinesia is related to a phenotype modification of the striatal neurons. However, this study supports the concept of axonal collateralization of striatofugal cells that project to both globus pallidus pars externa and globus pallidus pars interna. Striatofugal pathways are not as segregated in the primate as previously considered.

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Detection of human T-lymphotropic virus type I p40^taxprotein in cerebrospinal fluid cells from patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis

Cited by 62 publications

References 14 publications

Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy

Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy

HTLV-1 induces a Th1-like state in CD4+CCR4+ T cells

Phenotype of Striatofugal Medium Spiny Neurons in Parkinsonian and Dyskinetic Nonhuman Primates: A Call for a Reappraisal of the Functional Organization of the Basal Ganglia

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Detection of human T-lymphotropic virus type I p40taxprotein in cerebrospinal fluid cells from patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis

Cited by 62 publications

References 14 publications

Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy

Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy

HTLV-1 induces a Th1-like state in CD4+CCR4+ T cells

Phenotype of Striatofugal Medium Spiny Neurons in Parkinsonian and Dyskinetic Nonhuman Primates: A Call for a Reappraisal of the Functional Organization of the Basal Ganglia

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Detection of human T-lymphotropic virus type I p40^taxprotein in cerebrospinal fluid cells from patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis