Search Results (27)

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

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

Genetic alterations are well known to be related to the pathogenesis and prognosis of papillary thyroid carcinoma (PTC). Some miRNA expression dysregulations have previously been described in the context of cancer development including thyroid carcinoma. In our study, we performed original molecular diagnostics on tissue samples related to our own patients. We aimed to identify all dysregulated miRNAs in potential association with PTC development via sequencing much higher numbers of control-matched PTC tissue samples and analyzing a wider variety of miRNA types than previous studies. We analyzed the expression levels of 2656 different human miRNAs in the context of 236 thyroid tissue samples (118 tumor and control pairs) related to anonymized PTC cases. Also, KEGG pathway enrichment analysis and GO framework analysis were used to establish the links between miRNA dysregulation and certain biological processes, pathways of signaling, molecular functions, and cellular components. A total of 30 significant differential miRNA expressions with at least ±1 log₂ fold change were found related to PTC including, e.g., miR-551b, miR-146b, miR-221, miR-222, and miR-375, among others, being highly upregulated, as well as miR-873 and miR-204 being downregulated. In addition, we identified miRNA patterns in vast databases (KEGG and GO) closely similar to that of PTC including, e.g., miRNA patterns of prostate cancer, HTLV infection, HIF-1 signaling, cellular responses to growth factor stimulus and organic substance, and negative regulation of gene expression. We also found 352 potential associations between certain miRNA expressions and states of clinicopathological variables. Our findings—supported by the largest case number of original matched-control PTC–miRNA relation research—suggest a distinct miRNA expression profile in PTC that could contribute to a deeper understanding of the underlying molecular mechanisms promoting the pathogenesis of the disease. Moreover, significant miRNA expression deviations and their signaling pathways in PTC presented in our study may serve as potential biomarkers for PTC diagnosis and prognosis or even therapeutic targets in the future. Full article

HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a progressive non-remitting and incapacitating disease more frequently seen in women and with a patchy worldwide distribution. HAM/TSP develops in a small percentage of HTLV-1-infected individuals during their lifetime and etiologic factors for disease progression are still unclear. This study aims to describe the first case series of the progression of HAM/TSP in relation to pregnancy. Between January and March of 2012, we reviewed medical charts of women with HAM/TSP currently enrolled in the HTLV-1 cohort at the institute of tropical medicine of Cayetano Heredia University. Inclusion criteria included having a diagnosis of HAM/TSP according to the WHO guidelines and self-reported initial symptoms of HAM/TSP during pregnancy or within six months of delivery. Fifteen women reported having had symptoms compatible with HAM/TSP within four months of delivery. Among them, ten women had no symptoms before pregnancy and reported gait impairment after delivery. Five women with mild gait impairment before pregnancy noticed a worsening of their symptoms after delivery. Symptoms worsened after successive pregnancies. Recent studies have shown that HTLV-1 infection induces a strong T cell-mediated response and that the quality of this response plays a role in HAM/TSP pathogenesis. The relative immunosuppression during pregnancy, including blunting of the T-cell response, might allowed in certain women enhanced replication of HTLV-1 and disease progression in the postpartum. This is the first study looking specifically at HAM/TSP and pregnancy and the number of cases is remarkable. Further prospective studies of HTLV-1-infected women assessing immune markers during pregnancy are warranted. Breastfeeding was the main route of transmission. Strategies to prevent vertical transmission need to be evaluated in HTLV-1 endemic countries of Latin America. Full article

HIV-1, Hepatitis B and HTLV-1 have similar risk factors and shared routes of transmission and MSM are disproportionately affected by HIV. The aim of the study was to determine the prevalence of HTLV-1 and HBsAg positivity at initial enrolment among MSM attending a large HIV Clinic in Trinidad. Chart reviews were conducted between 2 and 15 January 2024, among self-identified MSM and a comparative group of randomly selected self-identified heterosexual males where sociodemographic, clinical and laboratory data were collected and analysed using SPSS Version 25. During the period April 2002–31 October 2023, in total there were 10,424 patients registered at the clinic, of whom 1255 (12.0%) were self-identified MSM, with an age range of 19–85 years and a median age of 40 years. There were 1822 randomly selected heterosexual males, with an age range of 18–94 years old and a median age of 52 years. Among the MSM, there were 21 (1.67%) patients who were HIV-1/HTLV-1-coinfected, 64 (5.10%) who were HIV-1/HBsAg-coinfected and two (0.16%) who were coinfected with all three viruses (HIV-1/HTLV-1/HBsAg) as compared to 47 ((2.58%) HIV-1/HTLV-1-coinfected (p = 0.12), 69 (3.79%) HIV-1/HBsAg-coinfected (p = 0.10) and three (0.16%) patients coinfected with all three viruses among the heterosexual males. There were no patients with HTLV-1-related diseases among the HIV-1/HTLV-1-coinfected patients and there were no deaths from chronic liver disease in patients coinfected with HIV-1/HBsAg. Despite the availability of an efficacious vaccine, there is a prevalence of hepatitis B of 5.1% among MSM attending the HIV Clinic in Trinidad; therefore, programmes to increase health literacy, screening and immunization are urgently needed. Full article

Among the human T-lymphotropic virus (HTLV) types, HTLV-1 is the most prevalent, and it has been linked to a spectrum of diseases, including HAM/TSP, ATLL, and hyperinfection syndrome or disseminated strongyloidiasis. There is currently no globally standard first-line treatment for HTLV-1 infection and its related diseases. To address this, a comprehensive review was conducted, analyzing 30 recent papers from databases PubMed, CAPES journals, and the Virtual Health Library (VHL). The studies encompassed a wide range of therapeutic approaches, including antiretrovirals, immunomodulators, antineoplastics, amino acids, antiparasitics, and even natural products and plant extracts. Notably, the category with the highest number of articles was related to drugs for the treatment of ATLL. Studies employing mogamulizumab as a new perspective for ATLL received greater attention in the last 5 years, demonstrating efficacy, safe use in the elderly, significant antitumor activity, and increased survival time for refractory patients. Concerning HAM/TSP, despite corticosteroid being recommended, a more randomized clinical trial is needed to support treatment other than corticoids. The study also included a comprehensive review of the drugs used to treat disseminated strongyloidiasis in co-infection with HTLV-1, including their administration form, in order to emphasize gaps and facilitate the development of other studies aiming at better-directed methodologies. Additionally, docking molecules and computer simulations show promise in identifying novel therapeutic targets and repurposing existing drugs. These advances are crucial in developing more effective and targeted treatments against HTLV-1 and its related diseases. Full article

Adult T cell leukemia (ATL) is an aggressive hematologic disease caused by human T cell leukemia virus type 1 (HTLV-1) infection. Various animal models of HTLV-1 infection/ATL have been established to elucidate the pathogenesis of ATL and develop appropriate treatments. For analyses employing murine models, transgenic and immunodeficient mice are used because of the low infectivity of HTLV-1 in mice. Each mouse model has different characteristics that must be considered before use for different HTLV-1 research purposes. HTLV-1 Tax and HBZ transgenic mice spontaneously develop tumors, and the roles of both Tax and HBZ in cell transformation and tumor growth have been established. Severely immunodeficient mice were able to be engrafted with ATL cell lines and have been used in preclinical studies of candidate molecules for the treatment of ATL. HTLV-1-infected humanized mice with an established human immune system are a suitable model to characterize cells in the early stages of HTLV-1 infection. This review outlines the characteristics of mouse models of HTLV-1 infection/ATL and describes progress made in elucidating the pathogenesis of ATL and developing related therapies using these mice. Full article

The present study sought to search for the immunodominance related to the N-terminal, Central and C-terminal regions of HTLV-1 Tax using novel, cutting-edge peptide microarray analysis. In addition, in silico predictions were performed to verify the presence of nine amino acid peptides present along Tax restricted to the human leukocyte antigen (HLA)-A2.02*01 haplotype, as well as to verify the ability to induce pro-inflammatory and regulatory cytokines, such as IFN-γ and IL-4, respectively. Our results indicated abundant dose-dependent reactivity for HLA-A*02:01 in all regions (N-terminal, Central and C-terminal), but with specific hotspots. Furthermore, the results of fold-change over the Tax^11–19 reactivity obtained at lower concentrations of HLA-A*02:01 reveal that peptides from the three regions contain sequences that react 100 times more than Tax^11–19. On the other hand, Tax^11–19 has similar or superior HLA-A*02:01 reactivity at higher concentrations of this haplotype. The in silico analysis showed a higher frequency of IFN-γ-inducing peptides in the N-terminal portion, while the C-terminal portion showed a higher frequency of IL-4 inducers. Taken together, these results shed light on the search for new Tax immunodominant epitopes, in addition to the canonic Tax^11–19, for the rational design of immunomodulatory strategies for HTLV-1 chronic diseases. Full article

Psoriasis is a persistent T-cell-supported inflammatory cutaneous disorder, which is defined by a significant expansion of basal cells in the epidermis. Cell cycle and STAT genes that control cell cycle progression and viral infection have been revealed to be comorbid with the development of certain cancers and other disorders, due to their abnormal or scanty expression. The purpose of this study is to evaluate the expression of certain cell cycle and STAT1/3 genes in psoriasis patients and to determine the types of comorbidities associated with these genes. To do so, we opted to adopt the in silico methodology, since it is a quick and easy way to discover any potential comorbidity risks that may exist in psoriasis patients. With the genes collected from early research groups, protein networks were created in this work using the NetworkAnalyst program. The crucial hub genes were identified by setting the degree parameter, and they were then used in gene ontology and pathway assessments. The transcription factors that control the hub genes were detected by exploring TRRUST, and DGIdb was probed for remedies that target transcription factors and hubs. Using the degree filter, the first protein subnetwork produced seven hub genes, including STAT3, CCNB1, STAT1, CCND1, CDC20, HSPA4, and MAD2L1. The hub genes were shown to be implicated in cell cycle pathways by the gene ontology and Reactome annotations. The former four hubs were found in signaling pathways, including prolactin, FoxO, JAK/STAT, and p53, according to the KEGG annotation. Furthermore, they enhanced several malignancies, including pancreatic cancer, Kaposi’s sarcoma, non-small cell lung cancer, and acute myeloid leukemia. Viral infections, including measles, hepatitis C, Epstein–Barr virus, and HTLV-1 and viral carcinogenesis were among the other susceptible diseases. Diabetes and inflammatory bowel disease were conjointly annotated. In total, 129 medicines were discovered in DGIdb to be effective against the transcription factors BRCA1, RELA, TP53, and MYC, as opposed to 10 medications against the hubs, STAT3 and CCND1, in tandem with 8 common medicines. The study suggests that the annotated medications should be tested in suitable psoriatic cell lines and animal models to optimize the drugs used based on the kind, severity, and related comorbidities of psoriasis. Furthermore, a personalized medicine protocol must be designed for each psoriasis patient that displays different comorbidities. Full article

(1) Background: Tropical spastic paraparesis (TSP/HAM) associated with the T cell lymphotropic virus in type I humans (HTLV-1) is a slow, chronic, and progressive disease that causes balance changes. TSP/HAM diagnosis can be classified as probable, possible, and definite. We compared the static balance control of HTLV-1-infected patients with different TSP/HAM diagnosis. (2) Methods: Our sample consisted of 13 participants infected with HTLV-1 and 16 healthy participants. The center of pressure was recorded using a force platform with open and closed eyes. We divided the recordings into three intervals, period T1 (corresponds to the first 10 s); period T2 (from 10 to 45 s); period T3 (from 45 to 55 s). (3) Results: Eight participants infected with HTLV-1 were classified as probable TSP/HAM and five participants infected with HTLV-1 were classified as definite TSP/HAM. There was a significant increase in postural instability in patients with definite PET/MAH considering the structural and global variables of body sway compared to the control and the probable TSP/HAM. (4) Conclusions: We concluded that the severity of balance is directly related to the degree of signs and symptoms of TSP/HAM. Full article

Genetic variations in components of the immune response seem to be an important factor that contributes to the manifestation of symptoms of some diseases related to HTLV-1 infection. Nerve growth factor (NGF) and the p75 neurotrophin receptor (p75^NTR) are related to the maintenance of neurons and the activation of the immune response. In this study, we evaluated the association of the NGF -198C/T, NGF Ala35Val, and p75^NTR Ser205Leu polymorphisms with HTLV-1 infection and plasma cytokine levels in 166 samples from individuals infected with HTLV-1 (59 symptomatic and 107 asymptomatic). The genotyping and quantification of the proviral load were performed by real-time PCR, and cytokine levels were measured by ELISA. The NGF -198C/T and NGF Ala35Val polymorphisms were not associated with HTLV-1 infection. The frequency of the Ser/Leu genotype of p75^NTR Ser205Leu was more frequent in the control group (p = 0.0385), and the Ser/Leu genotype and allele Leu were more frequent among the asymptomatic (p < 0.05), especially with respect to the HTLV-1-associated myelopathy (HAM) group (p < 0.05). The symptomatic showed a higher proviral load and higher TNF-α and IL-10 levels (p < 0.05). Asymptomatic carriers of the Ser/Leu genotype (p = 0.0797) had lower levels of proviral load and higher levels of TNF-α (p = 0.0507). Based on the results obtained, we conclude that the p75^NTR Ser205Leu polymorphism may be associated with reduced susceptibility to HTLV-1 infection, a lower risk of developing symptoms, including HAM, and better infection control. Full article

HTLV-1 uveitis (HU) is the third clinical entity to be designated as an HTLV-1-associated disease. Although HU is considered to be the second-most frequent HTLV-1-associated disease in Japan, information on HU is limited compared to that on adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). Recent studies have addressed several long-standing uncertainties about HU. HTLV-1-related diseases are known to be caused mainly through vertical transmission (mother-to-child transmission), but emerging HTLV-1 infection by horizontal transmission (such as sexual transmission) has become a major problem in metropolitan areas, such as Tokyo, Japan. Investigation in Tokyo showed that horizontal transmission of HTLV-1 was responsible for HU with severe and persistent ocular inflammation. The development of ATL and HAM is known to be related to a high provirus load and hence involves a long latency period. On the other hand, factors contributing to the development of HU are poorly understood. Recent investigations revealed that severe HU occurs against a background of Graves’ disease despite a low provirus load and short latency period. This review highlights the recent knowledge on HU and provides an update on the topic of HU in consideration of a recent nationwide survey. Full article

Human T-cell leukemia virus type 1 (HTLV-1) causes serious and intractable diseases in some carriers after infection. The elimination of infected cells is considered important to prevent this onset, but there are currently no means by which to accomplish this. We previously developed “virotherapy”, a therapeutic method that targets and kills HTLV-1-infected cells using a cytolytic recombinant vesicular stomatitis virus (rVSV). Infection with rVSV expressing an HTLV-1 primary receptor elicits therapeutic effects on HTLV-1-infected envelope protein (Env)-expressing cells in vitro and in vivo. Simian T-cell leukemia virus type 1 (STLV-1) is closely related genetically to HTLV-1, and STLV-1-infected Japanese macaques (JMs) are considered a useful HTLV-1 surrogate, non-human primate model in vivo. Here, we performed an in vitro drug evaluation of rVSVs against STLV-1 as a preclinical study. We generated novel rVSVs encoding the STLV-1 primary receptor, simian glucose transporter 1 (JM GLUT1), with or without an AcGFP reporter gene. Our data demonstrate that these rVSVs specifically and efficiently infected/eliminated the STLV-1 Env-expressing cells in vitro. These results indicate that rVSVs carrying the STLV-1 receptor could be an excellent candidate for unique anti-STLV-1 virotherapy; therefore, such antivirals can now be applied to STLV-1-infected JMs to determine their therapeutic usefulness in vivo. Full article

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that is the causative infectious agent of adult T-cell leukemia/lymphoma (ATL), an aggressive and fatal CD4⁺ T-cell malignancy, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic neurological disease. Disease progression in infected individuals is the result of HTLV-1-driven clonal expansion of CD4⁺ T-cells and is generally associated with the activities of the viral oncoproteins Tax and Hbz. A closely related virus, HTLV-2, exhibits similar genomic features and the capacity to transform T-cells, but is non-pathogenic. In vitro, HTLV-1 primarily immortalizes or transforms CD4⁺ T-cells, while HTLV-2 displays a transformation tropism for CD8⁺ T-cells. This distinct tropism is recapitulated in infected people. Through comparative studies, the genetic determinant for this divergent tropism of HTLV-1/2 has been mapped to the viral envelope (Env). In this review, we explore the emerging roles for Env beyond initial viral entry and examine current perspectives on its contributions to HTLV-1-mediated disease development. Full article

Bovine leukaemia virus (BLV) is a deltaretrovirus that is closely related to human T-cell leukaemia virus types 1 and 2 (HTLV-1 and -2). It causes enzootic bovine leukosis (EBL), which is the most important neoplastic disease in cattle. Most BLV-infected cattle are asymptomatic, which potentiates extremely high shedding rates of the virus in many cattle populations. Approximately 30% of them show persistent lymphocytosis that has various clinical outcomes; only a small proportion of animals (less than 5%) exhibit signs of EBL. BLV causes major economic losses in the cattle industry, especially in dairy farms. Direct costs are due to a decrease in animal productivity and in cow longevity; indirect costs are caused by restrictions that are placed on the import of animals and animal products from infected areas. Most European regions have implemented an efficient eradication programme, yet BLV prevalence remains high worldwide. Control of the disease is not feasible because there is no effective vaccine against it. Therefore, detection and early diagnosis of the disease are essential in order to diminish its spreading and the economic losses it causes. This review comprises an overview of bovine leukosis, which highlights the epidemiology of the disease, diagnostic tests that are used and effective control strategies. Full article