Search Results (311)

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article

Human T-cell lymphotropic virus (HTLV), a retrovirus associated with severe conditions such as leukemia/lymphoma and myelopathy, exhibits variable global prevalence, with higher rates observed in regions such as northeastern Brazil and sub-Saharan Africa. While intrauterine transmission can occur via viral expression in placental tissue and contact with umbilical cord blood, the predominant route is vertical transmission through breastfeeding. Diagnostic testing, particularly serological screening with ELISA and confirmatory methods such as Western blot and PCR, is essential for early detection during pregnancy. The implementation of prenatal screening programs, as seen in Japan and Brazil, has proven effective in reducing vertical transmission by guiding interventions such as breastfeeding cessation in infected mothers. Beyond clinical implications, the psychosocial impact on affected pregnant women highlights the need for an interdisciplinary approach. Although the association between HTLV infection and adverse obstetric outcomes remains controversial, studies suggest increased risks of preterm birth, low birth weight, and other neonatal complications. Given the importance of early diagnosis and prevention, universal prenatal screening protocols represent a critical strategy to reduce viral transmission and its long-term consequences. Full article

Background/Objectives: Since the World Health Organization (WHO) recommended HIV self-testing as an alternative to traditional facility-based testing in 2016, it has been increasingly adopted worldwide. This study aimed to evaluate the performance of the ConfiSign HIV Self-Test (GenBody Inc., Republic of Korea), a newly developed blood-based immunochromatographic assay for the qualitative detection of total antibodies (IgG and IgM) against HIV-1/HIV-2. Methods: The evaluation included four components: (1) retrospective analysis of 1400 archived serum samples (400 HIV-positive and 1000 HIV-negative samples), (2) prospective self-testing by 335 participants (112 HIV-positive participants and 223 individuals with an unknown HIV status, including healthy volunteers), (3) assessment using seroconversion panels and diverse HIV subtypes, and (4) analytical specificity testing for cross-reactivity and interference. The Elecsys HIV combi PT and Alinity I HIV Ag/Ab Combo assays were used as reference assays. Results: In retrospective testing, the ConfiSign HIV Self-Test achieved a positive percent agreement (PPA) of 100%, a negative percent agreement (NPA) of 99.2%, and a Cohen’s kappa value of 0.986, showing excellent agreement with the reference assays. In the prospective study, the test showed 100% sensitivity and specificity, with a low invalid result rate of 1.8%. All HIV-positive samples, including those with low signal-to-cutoff (S/Co) values in the Alinity I assay, were correctly identified. The test also reliably detected early seroconversion samples and accurately identified a broad range of HIV-1 subtypes (A, B, C, D, F, G, CRF01_AE, CRF02_AG, and group O) as well as HIV-2. No cross-reactivity or interference was observed with samples that were positive for hepatitis viruses, cytomegalovirus, Epstein–Barr virus, varicella zoster virus, influenza, HTLV-1, HTLV-2, or malaria. Conclusions: The ConfiSign HIV Self-Test demonstrated excellent sensitivity, specificity, and robustness across diverse clinical samples, supporting its reliability and practicality as a self-testing option for HIV-1/2 antibody detection. Full article

T-cell receptors (TCRs) exhibit degeneracy, enabling individual TCRs to recognize multiple altered peptide ligands (APLs) derived from a single cognate antigen. This characteristic has been involved in the pathogenesis of autoimmune diseases through cross-reactivity between microbial and self-antigens. Cytotoxic T lymphocytes (CTLs), which recognize peptide–MHC class I complexes via TCRs, play a critical role in the immune response against viral infections. However, the extent to which TCR degeneracy within a population of virus-specific CTLs contributes to effective viral control remains poorly understood. In this study, we investigated the magnitude and functional relevance of TCR degeneracy in CTLs targeting an immunodominant epitope of human T-cell leukemia virus type 1 (HTLV-1) in patients with HTLV-1-associated myelopathy (HAM). Using peripheral blood mononuclear cells (PBMCs) from these patients, we quantified TCR degeneracy at the population level by comparing CTL responses to a panel of APLs with responses to the cognate epitope. Our findings demonstrated that increased TCR degeneracy, particularly at the primary TCR contact residue at position 5 of the antigen, was inversely correlated with HTLV-1 proviral load (p = 0.038, R = −0.40), despite similar functional avidity across patient-derived CTLs. Viral sequencing further revealed that CTLs with high TCR degeneracy exerted stronger selective pressure on the virus, as indicated by a higher frequency of nonsynonymous substitutions within the epitope-encoding region in patients with highly degenerate TCR repertoires. Moreover, TCR degeneracy was positively correlated with the recognition rate of epitope variants (p = 0.018, R = 0.76), suggesting that CTLs with high TCR degeneracy exhibited enhanced recognition of naturally occurring epitope variants compared to those with low TCR degeneracy. Taken together, these results suggest that virus-specific CTLs with high TCR degeneracy possess superior antiviral capacity, characterized by broadened epitope recognition and more effective suppression of HTLV-1 infection. To our knowledge, this is the first study to systematically quantify TCR degeneracy in HTLV-1-specific CTLs and evaluate its contribution to viral control in HAM patients. These findings establish TCR degeneracy as a critical determinant of antiviral efficacy and provide a novel immunological insight into the mechanisms of viral suppression in chronic HTLV-1 infection. Full article

Human T-lymphotropic virus 1 (HTLV-1) infection has been associated with inflammatory, autoimmune, and lymphoproliferative diseases with a wide spectrum of clinical manifestations. Among patients with inflammatory rheumatological disease manifestations, cases of rheumatoid arthritis, Sjögren’s syndrome, polymyositis, and fibromyalgia, among others, have been reported. Another common feature of rheumatological diseases is the presence of joint manifestations, such as arthralgia and arthritis. In the present study, we sought to determine the laboratory profile and clinical rheumatological manifestations of people living with HTLV-1/2 residing in a metropolitan area in the Brazilian Amazon. A total of 957 individuals were screened for HTLV-1/2 infection by enzyme-linked immunosorbent assay (ELISA), and samples from seropositive individuals were subjected to infection confirmation by Western blotting or quantitative polymerase chain reaction (qPCR). Individuals with confirmed HTLV-1 and HTLV-2 infection were clinically evaluated for signs and symptoms of rheumatological diseases. Of the 957 individuals tested, 69 were positive for HTLV-1/2 infection, with 56 confirmed cases of HTLV-1 infection (5.9%), 12 of HTLV-2 infection (1.2%), and 1 classified as undetermined (0.1%). After clinical screening, 15 infected individuals with complaints suggestive of rheumatological disease were selected for evaluation by a rheumatologist (11 with HTLV-1 infection (1.1%) and 4 with HTLV-2 infection (0.4%)). The predominant pain pattern was symmetrical polyarthralgia, with large joints predominantly being affected. The diseases diagnosed were psoriatic arthritis, osteoarthritis, fibromyalgia, and regional pain syndromes. Antinuclear antibody (ANA) positivity was observed in two patients. Our findings confirm that HTLV-1 infection is associated with rheumatological disease manifestations and highlight the novel finding of cases of HTLV-2 infection in patients with rheumatoid arthritis symptoms. Full article

Background/Objectives: This study aimed to explore how HTLV-2 infection affects the production of broadly neutralizing antibodies (bNAbs) in persons with HIV-1 (PWH) and to assess the impact of boosted protease inhibitors (PIs). Methods: We evaluated broadly neutralizing antibody (bNAb) activity in 65 PWH, which included 27 who were also co-infected with HTLV-2. All participants were former injection drug users with HCV antibodies and were receiving suppressive antiretroviral therapy (ART). Neutralizing activity was assessed against six recombinant HIV-1 viruses that represent five different subtypes. B cell subsets were also analyzed. Results: HTLV-2 co-infection and the lack of ritonavir-boosted protease inhibitors (r-PIs) were both independently associated with higher neutralization scores (p = 0.017 and p = 0.005, respectively). Among those not on r-PIs, individuals co-infected with HTLV-2 showed significantly higher neutralization scores (p = 0.027) and a broader neutralization breadth (83.4% vs. 48.5%, p = 0.015) compared to those infected only with HIV-1. Additionally, HTLV-2 co-infected individuals had more resting memory B cells (p = 0.001) and fewer activated memory B cells (p = 0.017) than the HIV-1 mono-infected individuals. In our multivariate analysis, only HTLV-2 co-infection remained independently associated with neutralization scores (p = 0.027). Elite neutralizers (with a breadth score of ≥10) had more naive B cells and fewer resting memory B cells compared to those with weaker neutralization in both groups. Conclusions: Co-infection with HTLV-2 enhances bNAb production in PWH on suppressive ART and, in particular, in the absence of r-PI regimens. The prominent neutralizing activity corresponded with B cell subset distributions. The results suggest the complexity regarding the interaction between viral co-infections, antiretroviral regimens, and humoral immune compartments and may inform further H1V-1 pathogenesis inquiries or the appropriate design of a vaccine. Full article

This descriptive, observational, cross-sectional study evaluated HTLV-1 and HTLV-2 infections in Ananindeua, northern Brazil. Individuals were screened for anti-HTLV-1/2 using ELISA (Murex HTLV-I + II, DiaSorin). Reactive or indeterminate samples underwent confirmation via Western blot (HTLV Blot 2.4 kit, MP Diagnostics) and/or RT-qPCR. A questionnaire examined behavioral and risk factors for HTLV-1/2 infection. HTLV-positive individuals received counseling, nurse follow-up, and specialized medical care. Among the 228 individuals investigated, 6 (2.7%) were infected with HTLV-1: 4 men (66.67%) and 2 women (33.33%), aged 51–73 years. The only significant risk factor observed was blood transfusion. Additionally, 80 other individuals residing in the municipality of Ananindeua independently visited the laboratory for an HTLV-1/2 diagnosis. Among them, 23 were diagnosed with HTLV-1 infection, and 1 with HTLV-2. Among the 30 positive individuals, 80% were asymptomatic, while 20% exhibited clinical manifestations associated with HTLV infection, including HAM and Sézary syndrome. These results indicate a notable prevalence of HTLV-1 infection in the municipality of Ananindeua emphasizing the significance of diagnosing the infection to assess its prevalence across the country accurately. Full article

Human T cell leukemia virus type 1 (HTLV 1) is an oncogenic retrovirus responsible for the development of adult T cell leukemia (ATL). The minus strand of HTLV-1 provirus encodes an oncoprotein named HTLV-1 bZIP factor (HBZ), which plays a pivotal role in viral replication and T cell proliferation. Of particular interest is the spliced HBZ isoform (sHBZ), which is predominantly expressed in ATL cells and localizes within the nucleolus, conferring immortalizing properties to T cells. Our previous study has shown that sHBZ colocalizes and associates with Nucleophosmin/B23, a nucleolar phosphoprotein with multiple functions. In this study, through an optimized nucleolar isolation method, we first confirmed sHBZ’s nucleolar localization via Western blotting in transfected HEK293T cells, chronically HTLV-1-infected T cell lines, and freshly infected HeLa cells. We further demonstrated that the sHBZ/B23 association predominantly occurs in the nucleolus by co-immunoprecipitation of cell fractions. Our study highlights the nucleolar localization of sHBZ and its possibly essential interaction with this nucleolar-residing protein, leading to cell immortalization. Full article

This research addresses IL-28B gene polymorphisms (rs12979860 and rs8099917) to determine their association with HTLV-1-related diseases; it aims to compare genotypic frequencies to identify predisposition or protection, considering population, disease, and controls. Given HTLV-1’s impact on immunity, this study seeks biomarkers for early diagnosis and intervention. A systematic search met inclusion criteria, such as open access bibliographic and experimental studies published in English between 2010 and 2024, and genetic factors linked to susceptibility to pathologies. Regarding exclusion criteria, bibliographic or experimental studies in organisms other than humans, unofficial sources, non-indexed journals, and scientific articles in languages other than English were ruled out. Statistical data analyses were assessed using meta-analysis, including forest plot and Q test of heterogeneity based on the I² statistics. The analyzed data indicate associations between genotypes, such as CT, GG, CC, and TT of the rs12979890 and rs8099917 polymorphisms and the predisposition to various diseases, such as HCV, arthropathy, HAM/TSP, cytomegalovirus and Crimean–Congo hemorrhagic fever associated with HTLV-1; however, the observed inconsistencies, such as high heterogeneity, and deficiency of related information limit the consolidation of the findings. Further research is needed to clarify IL-28B genotype interactions and disease susceptibility in HTLV-1 infections. Full article

Bovine leukemia virus (BLV) is classified as a Deltaretrovirus and shows close genomic and biological similarities with human T-cell leukemia viruses (HTLVs). It serves as the etiological agent for enzootic bovine leukosis (EBL), which stands as the most prevalent neoplastic disease affecting cattle globally. Additionally, BLV has been identified as a potential zoonotic pathogen, although the risk to human health remains a subject of ongoing research. The insidious nature of BLV lies in its predominantly subclinical presentation; the majority of BLV-infected cattle show no apparent symptoms. This subclinical nature poses challenges for disease detection and control, as infected animals can remain unnoticed carriers, contributing to the silent spread of the virus within herds. This characteristic also underscores the importance of surveillance and early detection strategies to monitor BLV prevalence and mitigate its spread. Despite concerted efforts in some regions to implement eradication programs, BLV continues to maintain a high prevalence worldwide. The persistence of BLV in cattle populations highlights the need for innovative and integrated approaches to control and manage the disease effectively. The development of a BLV vaccine represents a significant breakthrough in the fight against BLV transmission. A successful vaccine can not only reduce the incidence of BLV infection but also minimize the associated economic losses linked to reduced milk production, reproductive issues, and the premature culling of infected animals. Therefore, a comprehensive understanding of BLV, encompassing its origin, evolutionary patterns, epidemiology, risk factors, and control strategies, is pivotal. Such knowledge serves as the foundation for the development of effective vaccines, diagnostic tools, and control measures. Through this review, we aim to consolidate and present this multifaceted understanding of BLV, providing valuable insights and guidance for researchers, veterinarians, and policymakers involved in BLV prevention and control efforts globally. Full article

Human T-lymphotropic viruses (HTLVs) are deltaretroviruses infecting millions of individuals worldwide, with HTLV-1 and HTLV-2 being the most widespread and clinically relevant types. HTLV-1 is associated with severe diseases such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), while HTLV-2 shows a lower pathogenic potential, with occasional links to neurological disorders. HTLV-3 and HTLV-4, identified in Central Africa, remain poorly characterized but are genetically close to their simian counterparts, indicating recent zoonotic transmission events. HTLVs replicate through a complex cycle involving cell-to-cell transmission and clonal expansion of infected lymphocytes. Viral persistence is mediated by regulatory and accessory proteins, notably Tax and HBZ in HTLV-1, which alter host cell signaling, immune responses, and genomic stability. Integration of proviral DNA into transcriptionally active regions of the host genome may contribute to oncogenesis and long-term viral latency. Differences in viral protein function and intracellular localization contribute to the distinct pathogenesis observed between HTLV-1 and HTLV-2. Geographically, HTLV-1 shows endemic clusters in southwestern Japan, sub-Saharan Africa, the Caribbean, South America, and parts of the Middle East and Oceania. HTLV-2 is concentrated among Indigenous populations in the Americas and people who inject drugs in Europe and North America. Transmission occurs primarily via breastfeeding, sexual contact, contaminated blood products, and, in some regions, zoonotic spillover. Diagnostic approaches include serological screening (ELISA, Western blot, LIA) and molecular assays (PCR, qPCR), with novel biosensor and AI-based methods under development. Despite advances in understanding viral biology, therapeutic options remain limited, and preventive strategies focus on transmission control. The long latency period, lack of effective treatments, and global neglect complicate public health responses, underscoring the need for increased awareness, research investment, and targeted interventions. Full article

Human T-cell lymphotropic virus type 1 (HTLV-1) infection poses significant challenges to maternal and neonatal health, particularly in endemic regions. Vertical transmission, which occurs most commonly through prolonged breastfeeding and rarely during pregnancy, or childbirth, perpetuates the virus within families. This observational, retrospective study analyzed HTLV-1-infected and uninfected pregnant women admitted for delivery at a university maternity hospital in Salvador, Brazil (2020–2022). Medical records provided sociodemographic, clinical, and laboratory data. The HTLV-1 infection rate was 4.61 per 1000 deliveries. The sociodemographic characteristics were similar between infected (n = 17) and uninfected (n = 34) women. HTLV-1-positive women had higher rates of unplanned and undesired pregnancies. Adverse pregnancy outcomes were frequent in both groups (94.1% vs. 91.2%), but metabolic disorders and hypertension/eclampsia were more common among the infected women. Preterm birth and postpartum complications were also more frequent (17.6% vs. 5.9%, respectively), although the difference was not statistically significant. Breastfeeding initiation within the first hours of life was lower among exposed newborns (28.6% vs. 70%; p = 0.013). Neonatal characteristics did not differ significantly between the groups. These findings highlight critical gaps in reproductive health awareness and barriers to accessing preventive interventions. Further research on therapeutic strategies is urgently needed to support the World Health Organization’s (WHO) goal of eliminating HTLV-1 vertical transmission by 2030. Full article

The human retroviruses HIV and HTLV-1/HTLV-2 are transmitted through similar pathways but result in markedly different diseases. This review delineates the immune-mediated mechanisms by which HTLVs influence HIV pathology in co-infected individuals. In the context of HIV co-infection, HTLV-1/HTLV-2 alter the cellular microenvironment to enhance their own survival while simultaneously impeding the progression of HIV. Despite the extensive body of literature on the biological and clinical implications of retroviral co-infections, decades of research have been marred by controversy due to several flawed epidemiological studies and anecdotal reports lacking robust statistical and scientific backing. Nevertheless, recent systematic and well-designed research has led to a growing consensus supporting at least three key conclusions: (1) co-infections of HIV-1 and HTLV-1 are frequently observed in patients with elevated CD4⁺ T-cell counts who present with lymphoma or neurological complications; (2) HIV-1 and HTLV-2 co-infections have been associated in some instances with a “long-term non-progressor” phenotype; (3) the differential function and/or overexpression of the HTLV-1 and HTLV-2 Tax proteins are likely crucial in the clinical and immunologic outcomes of HIV/HTLV-1 and -2 co-infections. The present review will provide a comprehensive account of research on retroviral co-infections, focusing particularly on their clinical manifestations and associated pathological features. Full article

The human T-cell leukemia type-1 (HTLV-1) retrovirus establishes chronic life-long infection in a fraction of infected individuals associated with severe pathological conditions. Although the mechanism driving disease development is not fully understood, current evidence indicates the essential functions of viral regulatory proteins. Among these, the p13 protein has previously been shown to localize to the inner mitochondrial membrane in T cells, altering mitochondrial biology and T-cell function. While CD4⁺ T cells are the primary cell target of HTLV-1 infection, genomic viral DNA has also been detected in monocytes, macrophages, and dendritic cells, which orchestrate innate and adaptive immunity and play a critical role in protecting against virus-induce diseases by establishing the appropriate balance of pro and anti-inflammatory responses. Given the central role of mitochondria in monocyte differentiation, we investigated the effect of p13 in monocytes/macrophages and found that by localizing to mitochondria, p13 affects mitochondrial respiration. Moreover, we demonstrate that p13 expression affects macrophage polarization to favor the recruitment of CD4⁺ T cells, the primary target of the virus, potentially facilitating the spread of viral infection and the development of disease. Full article

The human T-cell lymphotropic viruses of type 1 and 2 (HTLV 1/2) are retroviruses with estimations of 10 million people infected worldwide. HTLV 1/2 viruses are endemic in South America where Indigenous and Afro American populations are considered of high risk. Although several case reports of HTLV 1/2 associated pathologies and some prevalence studies have been reported in Ecuador, the country lacks a national surveillance and control program, and no screening of blood or organ donors is currently done. We discuss the problems associated to HTLV 1/2 in Ecuador and propose a strategy to improve a surveillance and control program. Full article