Search Results (332)

HTLV-1 and HTLV-2 infections are associated with various neurological manifestations, particularly HTLV-1-associated myelopathy (HAM). This descriptive, cross-sectional observational study aimed to investigate and analyze the neurological manifestations in patients treated at the Service for the Care of People Living with HTLV (Serviço de Atendimento à Pessoa Vivendo com HTLV-SAPEVH) at the Federal University of Pará. A cohort of 957 individuals underwent screening for HTLV-1/2 infection using enzyme-linked immunosorbent assay (ELISA), with seropositive samples subsequently confirmed via Western blotting or quantitative polymerase chain reaction (qPCR). HTLV-1/2 infection was confirmed in 69 individuals. Of these, fifteen individuals—diagnosed with HTLV-1 (n = 11) or HTLV-2 (n = 4) infection—who presented with neurological complaints at the first nursing consultation, were referred to a neurologist for clinical evaluation of neurological signs and symptoms. Most of the patients were female (13), ranging from 33 to 80 years of age. Neurological symptoms were present in 86.7%, and included spasticity, paraparesis, chronic pain, both motor and sensory deficits, as well as urinary disorders, predominantly affecting the thoracic spinal cord and lower limbs. Urinary symptoms were observed in 77% of symptomatic patients, often preceding other neurological signs that suggest a role as “sentinel symptoms” in the clinical screening of HTLV carriers. The results demonstrated the presence of neurological impairment in patients infected with both HTLV-1 and HTLV-2, with motor symptoms ranging from moderate to advanced. In addition, cases of cranial nerve and upper limb involvement were reported, a finding that is rarely described in the literature. The study highlights the importance of neurological assessment as early as possible in patients infected with either HTLV-1 or HTLV-2 and suggests that sphincter dysfunctions can serve as early clinical markers of future neurological impairment. Full article

Co-infection with human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) and HIV is not routinely screened for, yet it may significantly influence clinical progression, mortality, and quality of life in affected individuals. This study aimed to estimate the prevalence of HTLV-1/2 co-infection among adults living with HIV and to identify associated epidemiological factors in the Peruvian Amazon. A cross-sectional study was conducted including patients receiving antiretroviral therapy through the multidisciplinary TARGA program in Iquitos, Peru, during the second quarter of 2013. Screening for HTLV-1/2 antibodies was performed using enzyme-linked immunosorbent assay, with reactive samples confirmed by Line Immunoassay. Demographic and behavioral variables were collected, and prevalence odds ratios with 95% confidence intervals were estimated using logistic regression models. Among the 284 patients included, 28 were co-infected with HIV and HTLV-1/2, resulting in a prevalence of 10% with a 95% confidence interval of 6.5 to 14.1. In multivariable analysis, age over 35 years and having more than 10 lifetime sexual partners were independently associated with co-infection, with prevalence odds ratios of 12.4 and 3.6, respectively. HTLV-1/2 co-infection was highly prevalent among people living with HIV in the Peruvian Amazon, and the main risk factors identified suggest that cumulative exposure and sexual behavior play a significant role in the joint transmission of both retroviruses, supporting the need to consider systematic HTLV screening in endemic settings. Full article

Hepatitis B virus (HBV) and human T-lymphotropic virus type 1 (HTLV-1) are blood-borne pathogens with overlapping transmission routes, resulting in an increased prevalence of HBV among individuals infected with HTLV-1. Notwithstanding the widespread application of mathematical modeling to the study of each virus in isolation, the within-host dynamics of HBV–HTLV-1 co-infection remain insufficiently characterized. This study introduces a novel within-host co-infection model that characterizes the interactions between HBV and HTLV-1, where HTLV-1 infects CD4⁺ T cells and HBV targets hepatocytes. A comprehensive qualitative analysis yields four threshold parameters ($R_i,i=1,2,3,4$) governing the existence and stability of equilibrium points, with global stability established using Lyapunov functions. Numerical simulations validate the analytical results, and sensitivity analysis identifies parameters that most strongly influence the basic reproduction numbers for HBV ($R_1$) and HTLV-1 ($R_2$) mono-infections. Our results corroborate that, in patients with HBV, the presence of HTLV-1 contributes to an elevated HBV viral load and CD4⁺ T cells play a crucial role in controlling HBV infection. Full article

Persistent oncovirus infections account for 15–20% of the global cancer burden, driving multiple forms of human cancer. To maintain persistent infection and spread, oncoviruses drive alterations in host cell metabolism, immune signaling, and cell-to-cell communication throughout tumor microenvironments. Accumulating evidence has indicated that these alterations occur in conjunction with a range of organelle remodeling events that can differ between “dormant” viral latency and active lytic replication. Throughout each phase of infection, oncoviruses alter the morphology, composition, and function of organelles to promote cellular survival and proliferation, while periodically supporting viral replication. Here, we review oncovirus-driven organelle remodeling strategies across distinct infection states, including viral latency, reactivation from latency, and chronic active replication. We focus on the molecular mechanisms by which oncovirus-driven organelle remodeling promotes cellular transformation, impedes immune responses, and facilitates virion assembly and egress. We also draw parallels between remodeling strategies employed by oncogenic and oncomodulatory viruses, emphasizing broadly conserved mechanisms across cancer-associated infections. Lastly, we highlight how studies of oncovirus organelle remodeling are critical for discovering vulnerabilities in both oncogenic virus infection and viral oncogenesis, with therapeutic potential for multiple cancers. Full article

Human T-cell lymphotropic virus type 1 (HTLV-1) can cause HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive neuroinflammatory disease that lacks noninvasive biomarkers. We used untargeted urine metabolomics with machine learning to profile 113 participants (39 with HAM, 17 with intermediate syndrome, 33 asymptomatic carriers, and 24 healthy controls). Gas chromatography–mass spectrometry identified 175 metabolites, 86 of which showed significant differences (fold change > 2, FDR p < 0.05). Multivariate analyses revealed distinct but partially overlapping metabolic profiles: sPLS-DA captured a reproducible yet moderately discriminative signal, while nonlinear machine learning models (Random Forest and SVM) achieved robust group separation, with HAM displaying a distinct metabolic signature. Key discriminators included Unknown_151, Unknown_127, histidine, alanine, and 4-hydroxyphenylacetic acid, which showed marked reductions in HAM and yielded ROC AUCs of 0.855–0.871. Pathway and disease enrichment analyses highlighted disturbances in amino acid metabolism, particularly beta-alanine and aromatic amino acids, along with disease signatures related to inherited amino acid handling disorders such as hyperlysinemia. These results demonstrate that urinary metabolomics combined with machine learning can identify potential noninvasive biomarkers for HAM and provide novel insights into HTLV-1-associated pathophysiology. Full article

HTLV-1 and HIV-1 represent biologically significant, structurally close, and equally problematic yet divergent human retroviruses. Although both infect CD4+ T cells and share similar structural elements, they differ markedly in genomic stability, transmission dynamics, clinical progression, and, most importantly, their transcriptional regulatory mechanisms. HTLV-1, an ancient virus with a limited global burden, often remains asymptomatic for decades before potentially causing ATL or HAM/TSP. Conversely, HIV-1, a relatively recent zoonotic transmission, undergoes rapid replication, exhibits high genetic diversity, and causes progressive immunodeficiency unless controlled by antiretroviral therapy (ART). At the molecular level, HTLV-1 maintains proviral latency through a balanced bidirectional transcription of regulatory genes (e.g., Tax and HBZ) that manipulate host transcription and immune evasion pathways, facilitating persistence and oncogenesis. HBZ and Tax were shown to contribute to driving the progressive acquisition of Treg-like and HLA class II phenotype in chronically activated CD4+ T-cells, promoting tolerogenic antigen presentation and immune evasion in ATL cells. This well-controlled differential expression of HTLV-1 regulatory genes is attributed to multiple intragenic virus regulatory mechanisms, which will be discussed in this review. In contrast, HIV-1 transcription is driven by a tightly regulated 5′ LTR promoter involving host factors such as NF-κB, Sp1, AP-1, and NFAT, among others, with strong influence imposed by the landscape of the provirus integration site, playing a pivotal role in latency and reactivation. The distinct regulatory circuitry of each virus suggests a key difference in their essential regulation, with HTLV-1 primarily relying on intragenic mechanisms, while HIV-1 relies more heavily on interactions with the surrounding host environment to control its expression. This difference underscores unique therapeutic challenges in managing viral latency, persistence, and pathogenesis. Full article

Among the metal-derived complexes, recently, tin derivatives have been investigated as promising anti-cancer drug candidates. Our previous study showed that the tin-based compound Bu₃SnOCOCF₃ (TBT) exerts cytotoxic activity on solid tumor cell lines. In the present study, the effects of TBT were evaluated in vitro on HTLV-1-infected human lymphocytic cell lines at different stages of viral transformation, consisting of IL-2-dependent (PB2/IL-2) and IL-2-independent (PB2/NO-IL-2) cells, generated in our laboratory by HTLV-1 in vitro infection of lymphocytes from the same donor, and the C91/PL cell line established by co-cultivation with T cells from a patient with HTLV-1-positive leukemia. TBT induced a reliable and reproducible dose-dependent inhibition of metabolic activity and viability in the HTLV-1-infected cells. The effect was cell-type-dependent, with C91/PL cells being quite resistant. An investigation into the cytotoxic effects induced by TBT in HTLV-1-infected cells and data on caspase inhibitors/caspase activation indicated that apoptotic cell death was involved, but also that the possible involvement of other forms of cell death could not be excluded. Taken together, the results show for the first time that the tin-based compound, although not devoid of a certain cytotoxicity toward uninfected cells, can induce typical and potent effects on HTLV-1-infected cells. Full article

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy caused by persistent infection with human T-cell leukemia virus type 1 (HTLV-1). ATLL remains difficult to treat despite intensive chemotherapy, antiviral therapy, and hematopoietic stem cell transplantation. The limited durability of current treatment strategies highlights the need for mechanism-based therapeutic approaches. Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that regulates transcription, RNA splicing, DNA damage responses, and immune signaling through symmetric dimethylation of histone and non-histone substrates. PRMT5 is frequently overexpressed across hematologic and solid tumors. Preclinical studies indicate that PRMT5 expression is elevated during HTLV-1-mediated T-cell transformation and that pharmacologic inhibition of PRMT5 selectively impairs the survival and transformation of infected T cells in vitro and in vivo. In this review, we highlight the current understanding of PRMT5 biology in cancer, summarize preclinical studies supporting PRMT5 as a therapeutic target in ATLL, and discuss key challenges to future clinical translation. We also discuss emerging approaches such as rational combination therapies and tumor-selective PRMT5 inhibitors as potential paths toward treatment for ATLL. Full article

Human T-lymphotropic virus type 1 (HTLV-1), the first human retrovirus identified, is linked to adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. However, its post-transcriptional regulation remains poorly understood. Here, we used Oxford Nanopore direct RNA sequencing to profile the HTLV-1 transcriptome and epitranscriptome in MT2 cells. We identified 23 transcript isoforms, encompassing canonical and novel splice variants. Polyadenylation analysis revealed a predominant poly(A) tail length of around 50–100 nucleotides with transcript-specific variations. Distinct RNA modifications, including pseudouridine, N⁶-methyladenosine, and 5-methylcytidine, were enriched near the 3′ end and varied among transcript classes, with generally lower modification ratios in viral transcripts. These findings provide a more comprehensive map of HTLV-1 RNA splicing, polyadenylation, and modifications in MT2 cells, offering new insights into viral gene regulation and pathogenic mechanisms. Full article

Bovine leukemia virus (BLV) is a retrovirus infecting several bovid species, notably Bos taurus, where it fulfills Koch’s postulates for pathogenicity. The virus primarily targets B-lymphocytes, establishing lifelong infections that remain mostly asymptomatic but can progress to lymphocytosis or lymphoma. Transmission occurs through live infected cells via blood, milk, or transplacental routes. Despite a robust antiviral immunity, BLV replicates by producing virions (i.e., the infectious cycle) or inducing mitosis of infected cells (i.e., clonal expansion). The immune system effectively controls the infectious cycle but fails to impede clonal expansion, leading to chronic immune activation and immunosuppression. BLV modifies the transcriptome of the host cell by expressing oncogenic factors (Tax), viral microRNAs and antisense RNAs. Leukemogenesis arises from cumulative alterations of the virus (e.g., 5′-end deletions of the integrated provirus and histone modifications of the LTR promoter) and the host cell (e.g., genomic mutations and favorable chromatin integration). This model underscores a unique persistence strategy, linking chronic infection, immune evasion, and slow multistep oncogenesis in the bovine host. Full article

Background and Objectives: Transfusion-transmitted infections (TTIs) impose a considerable healthcare burden globally. Despite rigorous screening protocols, these infections can still be present among apparently healthy blood donors, potentially compromising the safety of transfusion recipients. Understanding the frequency of TTIs among blood donors is crucial for ensuring a healthy blood supply and gaining insights into the epidemiology of these infections within a community. Materials and Methods: The main objective of this study is to determine the frequency of TTIs among healthy blood donors, aged 18 to 60 years, at King Abdulaziz Hospital in Makkah City, Saudi Arabia. Data was collected retrospectively at the blood bank center from 1 January 2023, to 31 December 2023. Results: There were 8831 blood donors included. Saudi participants emerged as the dominant nationality, comprising 57% of the total sample (5036 out of 8831 donors). The prevalence of TTIs among blood donors varied according to the individual markers used. The overall TTI reactivity rates were low. Anti-HBc was the most common TTI-positive marker (7.5%), followed by syphilis (0.5%), HBV NAT (0.3%), HBsAg, and anti-HCV (0.3%). On the other hand, the lowest TTI-positive markers were HIV-1/-P2 and HTLV-1/-2 (0.04%). In Saudi participants, the most prevalent TTI marker was anti-HBc with a rate of 5.8% (293 out of 5036), followed by HBsAg (0.3%), syphilis (0.3%), and HBV NAT (0.2%). Conclusions: The present study found that HBV outperformed other TTI markers compared to the regional reports. However, in our research and the earlier reports, the rates of seropositive patients were noticeably low for HIV, HTLV, and malaria, while the rate for syphilis was higher, particularly among non-Saudi donors. NAT assays are crucial for screening blood donations for TTIs, which can help the early detection of infections and significantly reduce serological window periods. For a precise estimation of the frequency of TTIs, large prospective multicenter studies from various regions of the KSA are required. Full article

Clarifying the function of approximately 20,000 proteins encoded by the human genome is a key challenge in the fields of medicine and biology. However, many proteins remain uncharacterized. In this review, we introduce a challenge that uses adult T-cell leukemia/lymphoma (ATL) and proteomics to study human proteins of unknown function (PUFs). The characteristic properties of ATL cells are as follows: ATL cells (1) are infected with virus, (2) are derived from CD4⁺ T cells, (3) are generated via multi-stage carcinogenesis, (4) have flower-like nuclei, and (5) are highly infiltrative in the aggressive type. Given that ATL cells have contributed to impressive basic research, such as the discovery of HTLV-1 as a human cancer virus and interleukin-2 (IL-2) receptor α chain (IL-2Rα)/CD25, which is used for identifying regulatory T (Treg) cells, ATL cell lines could still be considered an attractive research tool. Furthermore, the “Unknome database” is useful for examining function-unknown degrees of proteins of interest using known scores based on Gene Ontology (GO) annotations and protein analysis through evolutionary relationships (PANTHER). Combining ATL proteomic data obtained by us with the “Unknome database” is expected to contribute not only to investigating the pathogenetic mechanism of ATL but also to clarifying the functions of PUFs. Full article

The prevalence of Human T-cell Lymphotropic Virus (HTLV) infections in Grenada has not been published since 2013. This study aimed to determine the combined seroprevalence and trends in HTLV-1 and HTLV-2 among pregnant women in Grenada from 2015 to 2024. Data were analyzed to determine the overall combined seroprevalence, observed trends, and public health implications over time. Data obtained from the Ministry of Health, Grenada, were analyzed to determine and compare the annual combined seroprevalence rate and the prevalence by age group and by health district during 2015–2024. Every pregnant woman included in the analysis was tested for HTLV-1 and -2 at the government’s public laboratories in Grenada. The overall rate of infection among persons tested was 1.45%. The highest prevalence of infection was among the 40+ (mature) age group. A significant association was found between HTLV infection and the mature age group (ϰ² = 7.981, p = 0.017, OR = 2.6, 95% CI: 1.1559–5.7122). Pregnant women aged 40 years and over are 2.6 times more at risk of infection compared to pregnant adolescents. Trends were also observed by health district, in which the prevalence rate was the highest in St. Patrick (2.18%) and the lowest in St. George (0.95%). Although there were no statistically significant associations observed between HTLV and the COVID-19 pandemic, there is a need for further research to understand the impact of emergencies on HTLV screening and prevalence. Further studies are also needed to identify factors and modes of HTLV transmission. Overall, these findings underscore the importance of targeted surveillance and tailored interventions to address HTLV transmission risks and protect population health in Grenada. Full article

Human T-lymphotropic virus type 1 (HTLV-1) infection is associated with a spectrum of clinical outcomes, ranging from lifelong asymptomatic carriage to severe conditions such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Although antibody responses are known to shape immune regulation, the functional relevance of IgG idiotype repertoires in HTLV-1 pathogenesis remains poorly understood. This study investigated the immunomodulatory effects of IgG from individuals with distinct HTLV-1 clinical outcomes. IgG was purified from pooled serum samples of asymptomatic carriers (ACs), HAM/TSP, and ATLL patients and used to stimulate peripheral blood mononuclear cells (PBMCs) from healthy donors. Cytokine production in CD4⁺, CD8⁺, and γδ T cells was assessed by flow cytometry. Additionally, proteome-wide IgG reactivity was evaluated using a human protein microarray encompassing over 21,000 proteins, and bioinformatic analyses were conducted to identify protein–protein interaction networks and tissue-specific autoreactivity. HAM/TSP-derived IgG selectively enhanced IFN-γ production in all T-cell subsets and suppressed IL-4 in CD4⁺ T cells. ATLL-derived IgG induced IL-9 and IL-13 production in CD4⁺ T cells, and both HAM/TSP and ATLL IgG elevated IL-13 levels in CD8⁺ T cells. Microarray data revealed distinct autoreactive IgG profiles across clinical groups, targeting immune-related proteins, apoptotic regulators, and proteins expressed in T cells, monocytes, and non-immune tissues such as brain and testis. Notably, no functional or structural clustering was observed in protein–protein interaction networks, suggesting these reactivities reflect complex, idiotype-specific immune alterations rather than compensatory responses. The present findings suggest that HTLV-1 infection may be associated with the development of distinct IgG repertoires that potentially modulate cytokine responses and exhibit broad reactivity toward human proteins. Such patterns could contribute to immune dysregulation and may partially explain the divergent clinical trajectories observed in HAM/TSP and ATLL. Further investigations are warranted to validate these observations at the individual level and to clarify their mechanistic relevance in disease progression. Full article

Since forkhead box P3 (FOXP3) is a hallmark of regulatory T (Treg) cells, the expansion of FOXP3⁺ adult T-cell leukemia/lymphoma (ATL) cells is believed to contribute to immune suppression and the pathogenesis of ATL. However, the mechanisms underlying the expansion of FOXP3⁺ ATL cells remain unclear. OX40, a co-stimulatory molecule, is expressed in ATL cells, and OX40 signaling has been shown to promote the differentiation and proliferation of Treg cells in mouse models. To investigate the mechanisms driving the expansion of FOXP3⁺ ATL cells, we examined the expression of OX40 and its ligand, OX40L. Our findings revealed that OX40 expression was elevated in patients with ATL and with a high frequency of FOXP3⁺ ATL cells. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) from patients with acute ATL cultured for 18 h demonstrated that FOXP3⁻ and FOXP3⁺ cells predominantly expressed OX40L and OX40, respectively. Furthermore, small interfering RNA-mediated FOXP3 knockdown in HTLV-1-infected cell lines increased OX40L expression. These results suggest that interactions between FOXP3⁻ OX40L⁺ cells and FOXP3⁺ OX40⁺ cells may promote the proliferation of FOXP3⁺ ATL cells. Full article