TLR signaling controls lethal encephalitis in WNV-infected brain.

Toll-like receptors (TLRs) are known to be activated in Central Nervous System (CNS) viral infections and are recognized to be a critical component in innate immunity. Several reports state a role for particular TLRs in various CNS viral infections. However, excessive TLR activation was previously reported by us in correlation with a pathogenic, rather than a protective, outcome, in a model of SIV encephalitis.

Impaired function of human T-lymphotropic virus type 1 (HTLV-1)-specific CD8+ T cells in HTLV-1-associated neurologic disease.

Despite abundant activated virus-specific cytotoxic T lymphocytes (CTLs), patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) showed a significantly higher frequency of infected T cells than did healthy virus carriers (HVCs). Here, we demonstrate that at a given proviral load, the frequency of CD8(+) T cells that are negative for specific costimulatory molecules was significantly higher in HAM/TSP than in age-matched HVCs and uninfected healthy controls (HCs), whereas the frequency of intracellular perforin-positive CD8(+) T cells was significantly lower in both HAM/TSP and HVCs than in HCs. An inverse correlation between HTLV-1 proviral load (PVL) and percent perforin-positive CD8(+) T cells were observed only in disease-protective allele HLA-A*02-positive HVCs, but not in HAM/TSP patients, whether HLA-A*02 positive or negative, nor in HLA-A*02-negative HVCs.

Clinical symptoms and the odds of human T-cell lymphotropic virus type 1-associated myelopathy/ tropical spastic paraparesis (HAM/TSP) in healthy virus carriers: application of best-fit logistic regression equation based on host genotype, age, and provirus load.

The authors have previously developed a logistic regression equation to predict the odds that a human T-cell lymphotropic virus type 1 (HTLV-1)-infected individual of specified genotype, age, and provirus load has HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in southern Japan. This study evaluated whether this equation is useful predictor for monitoring asymptomatic HTLV-1-seropositive carriers (HCs) in the same population. The authors genotyped 181 HCs for each HAM/TSP-associated gene (tumor necrosis factor [TNF]-alpha-863A/C, stromal cell-derived factor 1 (SDF-1) +801G/A, human leukocyte antigen [HLA]-A*02, HLA-Cw*08, HTLV-1 tax subgroup) and measured HTLV-1 provirus load in peripheral blood mononuclear cells using real-time polymerase chain reaction (PCR).

Association of AKT1 haplotype with the risk of schizophrenia in Iranian population.

AKT-glycogen synthase kinase 3beta (GSK3beta) signaling is a target of lithium and has been implicated in the pathogenesis of mood disorders and schizophrenia. AKT1 protein level is decreased in the peripheral lymphocytes and brains of schizophrenic patients. The SNP2/3/4 TCG haplotype of AKT1 was associated with schizophrenia in patients with Northern European origin.

Flow cytometry evaluation of the T-cell receptor Vbeta repertoire among human T-cell lymphotropic virus type-1 (HTLV-1) infected individuals: effect of interferon alpha therapy in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

Human T-cell lymphotropic virus type-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is chronic inflammatory disease of the spinal cord characterized by perivascular lymphocytic cuffing and parenchymal lymphocytic infiltration. In this study using flow cytometry, we have investigated the T-cell receptor (TCR) Vbeta repertoire of peripheral blood T lymphocytes in 8 HAM/TSP patients, 10 HTLV-1 infected healthy carriers, and 11 uninfected healthy controls to determine if there is a biased usage of TCR Vbeta. We found that TCR Vbeta7.

ApaI polymorphism of vitamin D receptor gene is associated with susceptibility to HTLV-1-associated myelopathy/tropical spastic paraparesis in HTLV-1 infected individuals.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is one outcome of human T-cell lymphotropic virus type-1 (HTLV-1) infection. It remains unknown why the majority of infected people remain healthy, whereas only approximately 2-3% of infected individuals develop the disease. The active form of vitamin D has immunomodulatory effects, and allelic variants of the vitamin D receptor (VDR) appear to be associated with differential susceptibility to several infectious diseases.

Differences in viral and host genetic risk factors for development of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis between Iranian and Japanese HTLV-1-infected individuals.

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disease observed only in 1-2 % of infected individuals. HTLV-1 provirus load, certain HLA alleles and HTLV-1 tax subgroups are reported to be associated with different levels of risk for HAM/TSP in Kagoshima, Japan. Here, it was determined whether these risk factors were also valid for HTLV-1-infected individuals in Mashhad in northeastern Iran, another region of endemic HTLV-1 infection.

High seroprotection rate induced by intradermal administration of a recombinant hepatitis B vaccine in young healthy adults: comparison with standard intramuscular vaccination.

Intradermal (ID) vaccination has been proposed as a cost-saving alternative for administration of Hepatitis B (HB) vaccine to implement of mass vaccination of high-risk groups, particularly in developing countries. Therefore, the effectiveness of ID vaccination needs to be evaluated and verified in different ethnic backgrounds. The present study is a randomized trail using a recombinant vaccine (Heberbiovac) to compare immunogenecity and safety of an intradermal low-dose (4 microg) with standard dose (20 microg) of intramuscular (IM) vaccination in healthy Iranian population.

Longer dinucleotide repeat polymorphism in matrix metalloproteinase-9 (MMP-9) gene promoter which correlates with higher HTLV-I Tax mediated transcriptional activity influences the risk of HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP).

Matrix metalloproteinase-9 (MMP-9) has been reported to be expressed in various inflammatory disorders including human T cell lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-I-infected T-cells expressed high levels of MMP-9 via viral transactivator Tax mediated activation of the MMP-9 promoter. To investigate whether the d(CA) repeat polymorphism in MMP-9 promoter affects the risk of developing HAM/TSP, we compared the allele frequencies between 200 HAM/TSP patients and 200 HTLV-I seropositive asymptomatic carriers (HCs).

Polymorphism in the interleukin-10 promoter affects both provirus load and the risk of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.

To investigate non-human leukocyte antigen candidate genes that influence the outcome of human T cell lymphotropic virus (HTLV) type I infection, we analyzed 6 single-nucleotide polymorphisms in the interleukin (IL)-10 promoter region in 280 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 255 HTLV-I-seropositive asymptomatic carriers from an area where HTLV-I is endemic. The IL-10 -592 A allele, which shows lower HTLV-I Tax-induced transcriptional activity than the C allele in the Jurkat T cell line, was associated with a >2-fold reduction in the odds of developing HAM/TSP (P=.011; odds ratio [OR], 0.

Serum concentration and genetic polymorphism in the 5'-untraslated region of VEGF is not associated with susceptibility to HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-I infected individuals.

HTLV-I- associated myelopathy/tropical spastic paraparesis (HAM/TSP) is one outcome of human T-cell lymphotropic virus type I (HTLV-I) infection. It remains unknown why the majority of infected people remain healthy whereas only approximately 2-3% of infected individuals develop the disease. Recently, it has been reported that increased plasma concentrations of VEGF were significantly related to high ATL cell infiltration, and the viral transactivator Tax activates the VEGF promoter, linking the induction of angiogenesis to viral gene expression.