HTLV-1関連脊髄症

BackgroundHuman T-cell lymphotropic virus type-1 (HTLV-1) is a retrovirus, mainly transmitted sexually, which causes adult T-cell leukaemia/lymphoma (ATLL) and HTLV-1 associated myelopathy (HAM). We aimed to update global HTLV-1 seroprevalence estimates, estimate the number of people living with HTLV-1 (PLHTLV) in England and Wales (E&W), and present E&W HTLV-1 surveillance data.MethodWe systematically reviewed countries with new HTLV-1 prevalence data since the 2015 European Centres for Disease Control report, including studies of adults in the general population, pregnant women and blood donors (Ovid MEDLINE, 01/09/2014-17/02/2023). Global seroprevalence and UK census data were used to estimate the number of PLHTLV in E&W for 1991 and 2021. Reference laboratory and hospital data were combined to describe patterns in new HTLV-1 diagnoses, and associated diseases, in 2013-2022, in E&W. Diagnoses in 2013-2022 were compared with 1993-1997 using Incidence Rate Ratios (IRR).ResultsNew seroprevalence data were found for Pakistan (0.19%, blood donors), Malawi (0.96%, healthy mothers), Jordan (0.00%, blood donors), Vietnam (0.00%, blood donors) and New Caledonia (0.60%, general population); 4/5 studies had a high risk of bias. Among 749 newly-diagnosed PLHTLV in E&W (2013-2022), most were women (58%, 434/749) and tested in London (64%, 480/749). Where recorded, Black Caribbean ethnicity predominated (61%, 228/373); 51% (396/619) were symptomatic, most commonly with ATLL (47%, 187/396). Comparing 1993-1997 with 2013-2022, the IRR was 1.26 (95%CI 1.09-1.46) overall, 1.60 (95%CI 1.17-2.23) for ATLL and 0.35 (95%CI 0.23-0.51) for HAM. Assuming all cases were due to migration from endemic countries, the estimated number of PLHTLV in E&W increased from 11,654 (range 3,804-19,504) in 1991 to 28,846 (range 10,365-47,328) in 2021.ConclusionsIn E&W, rising annual ATLL diagnoses are consistent with an increase in the estimate of the number of PLHTLV, necessitating enhanced public health interventions. The reduced IRR for HAM requires further investigation.

CRISPR technology is emerging as a promising therapeutic approach for eliminating chronic viral infections, such as herpesviruses and HIV. Here, for the first time, we demonstrate in vitro that CRISPR can be used to excise the HTLV-1 genome and reduce proviral loads in PBMCs from HAM/TSP (HTLV-1-associated myelopathy/tropical spastic paraparesis) patients. Single treatment with CRISPR-RNP (ribonucleoprotein) complexes composed of two gRNAs targeting the HTLV-1 env gene and 3'LTR sequences resulted in excision of a 2613 bp segment of the proviral genome, spanning tax and HBZ genes, without detectable off-target activity. Furthermore, CRISPR treatment led to over 50% reduction in proviral loads 5 days post-electroporation. Our data indicate that CRISPR-Cas9 gene editing can be used as a therapeutic strategy to eliminate HTLV-1 DNA from infected cells and may serve as a platform for curing HAM/TSP.

Human T-cell lymphotropic virus type 1 (HTLV-1) is a neglected pathogen with a heterogeneous global distribution. In low-prevalence areas, diagnostic testing is challenged by limited clinical awareness and the low positive predictive value of screening tests. We retrospectively analyzed 10,891 HTLV-1/2 test results from 7719 patient samples submitted to a specialized laboratory in Germany between 2004 and 2024. Antibody screening had a positive predictive value (PPV) of 31.7% for the Diasorin Murex HTLV I + II assay (39 of 123 reactive samples confirmed) and 34.5% for the Abbott Architect rHTLV-1/2 assay (67 of 194 reactive samples confirmed). Raising the sample/cutoff (s/co) threshold to ≥5 would have increased the PPV to >80%, with only two missed diagnoses per assay. HTLV-1 infection was confirmed in 124 carriers and HTLV-2 infection in three carriers. The vast majority of carriers originated from countries with higher endemicity. A delayed antibody response was observed in HTLV-1 infections via organ transplantation. In four patients with neurological disease, elevated HTLV-1/2-specific antibody indices showed antibody production in cerebrospinal fluid (CSF). HTLV-1 proviral load was measured in 83 carriers, with a median of 20,000 HTLV-1 DNA copies per 106 cells (interquartile range, 4000-119,600). Seventy-four percent (17/23) of high-dose intravenous immunoglobulin (IVIg) preparations contained HTLV-1/2 antibodies, which can lead to false-positive HTLV-1/2 antibody screening results in recipients without underlying infection. Therefore, HTLV-1/2 testing presents two major pitfalls: false-negative results in immunosuppressed patients and false-positive results following IVIg administration.

Human T-cell lymphotropic virus type 1 (HTLV-1) is a persistent human retrovirus associated with severe outcomes, most notably adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Despite lifelong infection, only a minority of carriers develop clinical disease, highlighting a decisive role for host genetic background in shaping viral control, immune activation, and pathogenic progression. This mini-review synthesizes evidence demonstrating how inherited host genetic variation and acquired somatic alterations influence HTLV infection outcomes. Polymorphisms in HLA class I and II genes critically modulate antigen presentation and cytotoxic or helper T-cell responses, thereby regulating proviral load and immune-mediated tissue damage. Variants in cytokine, chemokine, and innate restriction factor genes, including IL28B, IL8, TRIM5α, and APOBEC family members, further influence viral persistence and inflammatory risk. In parallel, accumulating somatic mutations in TP53, CCR4, JAK/STAT components, NOTCH1, and epigenetic regulators such as TET2 and KMT2D drive clonal expansion, genomic instability, and malignant transformation in ATLL. Together, these data support a continuum model in which inherited host genetics condition viral persistence and immune pressure, while acquired genetic and epigenetic lesions determine disease phenotype and severity. Integrating host genomics with viral genetics and clonal evolution analyses will be essential for developing predictive biomarkers and personalized therapeutic strategies for HTLV-associated diseases.

HTLV-1 infection causes chronic immune activation and a prolonged asymptomatic phase, but the functional features that define early disease remain unclear. We evaluated whether spontaneous proliferation (SP) and related functional immune parameters can distinguish clinical stages across the HTLV-1 spectrum. Spontaneous and mitogen-induced lymphoproliferation (PHA, anti-CD3), measured by CFSE dilution, and in vitro cell death, measured by cytometry, were assessed in 435 HTLV-1-infected individuals: asymptomatic carriers (AC, n = 303), individuals with intermediate syndrome (IS, n = 21), patients with HTLV-1-associated myelopathy (HAM, n = 94), adult T-cell leukemia/lymphoma (ATL, n = 17), and two control groups. Notably, SP levels divided the asymptomatic individuals in two subgroups: low-SP (24.5%), similar to the control groups, and high-SP (75.5%), resembling IS, HAM, and ATL patients. Additionally, high-SP AC and HTLV-1 symptomatic groups showed significantly reduced responses to PHA and increased spontaneous and PHA-stimulated cell death, all features also observed in IS, HAM, and ATL patients, while low-SP AC results mirrored those of control groups. This increased cell death is strongly correlated with upregulation of Fas and FasL, especially in lymphocytes from high-SP AC, which may underlie the chronic activation and susceptibility to cell death. These findings suggest that HTLV-1 AC comprises two distinct subgroups: one with high SP and cell death, likely due to ongoing viral activity and immune alterations, and another with low SP, low viral activity, and preserved immune homeostasis. Follow up studies of AC with these functional changes are needed to determine if they can help monitor disease progression and identify asymptomatic individuals at higher risk of clinical deterioration.