Sexual transmission of HTLV-1 resulting in uveitis with short-term latency and low proviral load.

Human T-cell Lymphotropic Virus Type 1 (HTLV-1) is traditionally linked to severe conditions such as adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy, and HTLV-1 uveitis, with vertical transmission, particularly mother to child thorough breastfeeding, considered the primary route. Despite efforts to reduce vertical transmission through antenatal screening in Japan, horizontal transmission has contributed to the rising prevalence of HTLV-1 in metropolitan areas. This case reports the youngest documented instance of HTLV-1 uveitis resulting from horizontal transmission through sexual contact in an 18-year-old woman. The patient presented with blurred vision in her right eye, and a comprehensive ophthalmologic examination identified vitreous opacity and retinal vasculitis. Serological tests confirmed HTLV-1 infection, with a proviral load of 2.66 copies per 100 peripheral blood mononuclear cells, measured by real-time PCR. A differential diagnosis confirmed HTLV-1 uveitis. Further family and partner investigations confirmed horizontal transmission, most likely through sexual contact. Over 6 years of follow-up, the patient experienced multiple recurrences of HTLV-1 uveitis and developed HTLV-1-associated keratopathy. This case highlights the potential for rapid disease progression with relatively low proviral loads and short latency, emphasizing the need for updated public health strategies for sexually active young populations.

Intrafamilial Transmission of HTLV-1 and HTLV-2 in Indigenous Peoples of the Brazilian Amazon: Molecular Characterization and Phylogenetic Analysis.

Human T-limphotropic virus 1 infection has a global distribution, with a high prevalence in some regions of Brazil and the world, while HTLV-2 infection is endemic mainly among indigenous people and drug users. To analyze intrafamilial transmission of HTLV-1/2 in five Kayapó indigenous peoples (Gorotire, Kararaô, Kokraimoro, Kubenkokre, and Xikrin do Bacajá), we investigated 1452 individuals who underwent serological and molecular tests. Among the 276 indigenous people with positive results, we identified intrafamily transmission in 42.7% of cases, representing 38 families. It was possible to suggest horizontal and vertical transmissions in 15.8% (6/38) and 47.4% (18/38) of the family groups, respectively. In 15.8%, it was not possible to suggest the route, which indicated that the transmission may have occurred through both vertical and horizontal routes. Through phylogenetic analyses, 35 samples positive for HTLV-2 were sequenced and classified as subtype 2c, and the two samples that tested positive for HTLV-1 were shown to belong to the cosmopolitan subtype, transcontinental subgroup (HTLV-1aA). This study confirms the intrafamilial transmission of HTLV-1/2 infection in indigenous people of the Brazilian Amazon, highlighting the importance of the sexual and mother-to-child transmission routes in maintaining the virus in these people.

The Global Prevalence of HTLV-1 and HTLV-2 Infections among Immigrants and Refugees-A Systematic Review and Meta-Analysis.

This is the first systematic review and meta-analysis to estimate the prevalence of human T-lymphotropic virus 1 and 2 (HTLV-1 and 2) infections among immigrants and refugees worldwide. PubMed/MEDLINE, Scopus, EMBASE, Web of Science, and Virtual Health Library (VHL) databases were searched for studies published from their inception to 6 January 2023. A meta-analysis using a generalized linear mixed model with a random effect was performed for HTLV-1 and HTLV-2. Subgroup analyses were performed based on the decade of study, sample size, confirmatory methods, region of study, risk group, and region of origin. Of the 381 studies initially identified, 21 were included. The pooled prevalence of HTLV-1 and HTLV-2 was 1.28% (95% CI: 0.58, 2.81) and 0.11% (95% CI: 0.04, 0.33), respectively. HTLV-1 prevalence differed significantly by region of origin, with the highest prevalence among those from the Western Pacific Region (7.27%; 95% CI: 2.94, 16.83). The subgroup analysis also showed significant differences between the estimates of HTLV-1 considering the decade of study, sample size, and region of study. For HTLV-2, significant differences were shown in relation to sample size, confirmatory methods, and risk group. The higher HTLV-1 prevalence found deserves public health attention in immigrant and refugee-receiving non-endemic countries.

Cognitive Assessment in HTLV-1 Patients Followed Up at a Reference Center in Salvador, Brazil.

INTRODUCTION: Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic to Brazil, and there is still no specific treatment for these patients. The literature shows that few studies have described the cognitive impairment associated with an HTLV-1 infection, with none of them examining the population of Salvador, where there are approximately forty thousand people infected with the virus. OBJECTIVES: To determine the prevalence of cognitive impairment among individuals with HTLV-1. In addition, investigate whether sociodemographic aspects, time since the diagnosis of infection, and the diagnosis of HTLV-Associated Myelopatia/Tropical Spastic Paraparesis (HAM/TSP) or depression are associated with cognitive impairment in this population. METHODS: This was an observational, cross-sectional study that consisted of consecutively approaching 100 HTLV-1 patients during outpatient care at a referral center followed by the administration of three questionnaires- the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and Beck's Depression Inventory. RESULTS: The prevalence of cognitive impairment found was 71% using the MMSE and 82% using the MoCA. There was a statistically significant association between the cognitive dysfunction and the variables of age and education according to the MoCA analysis but not the MMSE data. Diagnosis of HAM/TSP was correlated with cognitive impairment using the MMSE but not the MoCA. The prevalence of depression was 20%, and there was no association between cognitive impairment and depressive symptoms in these patients. CONCLUSIONS: The findings of this study demonstrate a correlation between cognitive dysfunction and HTVL-1 infection, with a more evident involvement of executive functions and memory. Larger studies are needed to clarify the association between cognitive dysfunction, age, education, and the diagnosis of HAM/TSP.

Diagnostic Value of Anti-HTLV-1-Antibody Quantification in Cerebrospinal Fluid for HTLV-1-Associated Myelopathy.

The diagnostic accuracy of cerebrospinal fluid (CSF) anti-human T-cell leukemia virus type I (HTLV-1) antibody testing for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM) remains unclear. Therefore, we measured the anti-HTLV-1 antibody levels in CSF using various test kits, evaluated the stability of CSF antibodies, and performed a correlation analysis using the particle agglutination (PA) method, as well as a receiver operating characteristic (ROC) analysis between patients with HAM and carriers. The CSF anti-HTLV-1 antibody levels were influenced by freeze-thaw cycles but remained stable when the CSF was refrigerated at 4 °C for up to 48 h. Measurements from 92 patients (69 patients with HAM and 23 carriers) demonstrated a strong correlation (r > 0.9) with the PA method across all six quantifiable test kits. All six test kits, along with CSF neopterin and CXCL10, exhibited areas under the ROC curve greater than 0.9, indicating a high diagnostic performance for HAM. Among these, five test kits, Lumipulse and Lumipulse Presto HTLV-I/II, HISCL-UD (a kit under development), HTLV-Abbott, and Elecsys HTLV-I/II, established a cutoff with 100% sensitivity and maximum specificity, achieving a sensitivity of 100% and a specificity ranging from 43.5% to 56.5%. This cutoff value, in combination with clinical findings, will aid in the accurate diagnosis of HAM.

Current State of Therapeutics for HTLV-1.

Human T cell leukaemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes lifelong infection in ~5-10 million individuals globally. It is endemic to certain First Nations populations of Northern and Central Australia, Japan, South and Central America, Africa, and the Caribbean region. HTLV-1 preferentially infects CD4+ T cells and remains in a state of reduced transcription, often being asymptomatic in the beginning of infection, with symptoms developing later in life. HTLV-1 infection is implicated in the development of adult T cell leukaemia/lymphoma (ATL) and HTLV-1-associated myelopathies (HAM), amongst other immune-related disorders. With no preventive or curative interventions, infected individuals have limited treatment options, most of which manage symptoms. The clinical burden and lack of treatment options directs the need for alternative treatment strategies for HTLV-1 infection. Recent advances have been made in the development of RNA-based antiviral therapeutics for Human Immunodeficiency Virus Type-1 (HIV-1), an analogous retrovirus that shares modes of transmission with HTLV-1. This review highlights past and ongoing efforts in the development of HTLV-1 therapeutics and vaccines, with a focus on the potential for gene therapy as a new treatment modality in light of its successes in HIV-1, as well as animal models that may help the advancement of novel antiviral and anticancer interventions.

HTLV-1 infected T cells cause bone loss via small extracellular vesicles.

Adult T cell leukaemia (ATL), caused by infection with human T- lymphotropic virus type 1 (HTLV-1), is often complicated by hypercalcemia and osteolytic lesions. Therefore, we studied the communication between patient-derived ATL cells (ATL-PDX) and HTLV-1 immortalized CD4+ T cell lines (HTLV/T) with osteoclasts and their effects on bone mass in mice. Intratibial inoculation of some HTLV/T leads to a profound local decrease in bone mass similar to marrow-replacing ATL-PDX, despite the fact that few HTLV/T cells persisted in the bone. To study the direct effect of HTLV/T and ATL-PDX on osteoclasts, supernatants were added to murine and human osteoclast precursors. ATL-PDX supernatants from hypercalcemic patients promoted the formation of mature osteoclasts, while those from HTLV/T were variably stimulatory, but had largely consistent effects between human and murine cultures. Interestingly, this osteoclastic activity did not correlate with expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand (RANKL), suggesting an alternative mechanism. HTLV/T and ATL-PDX produce small extracellular vesicles (sEV), known to facilitate HTLV-1 infection. We hypothesized that these sEV also mediate bone loss by targeting osteoclasts. We isolated sEV from both HTLV/T and ATL-PDX, and found they carried most of the activity found in supernatants. In contrast, sEV from uninfected activated T cells had little effect. Analysis of sEV (both active and inactive) by mass spectrometry and electron microscopy confirmed absence of RANKL and intact virus. Viral proteins Tax and Env were only present in sEV from the active, osteoclast-stimulatory group, along with increased representation of proteins involved in osteoclastogenesis and bone resorption. sEV from osteoclast-active HTLV/T injected over mouse calvaria in the presence of low-dose RANKL caused more osteolysis than osteoclast-inactive sEV or RANKL alone. Thus, HTLV-1 infection of T cells can cause release of sEV with strong osteolytic potential, providing a mechanism beyond RANKL production that modifies the bone microenvironment, even in the absence of overt leukaemia.

HTLV1 infection and long term association with liver function and lipid indices; 10 years' follow-up.

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) is a well-known retrovirus, particularly prevalent in northeastern Iran, where it is associated with a range of disorders, including liver dysfunction. Previous studies have demonstrated that HTLV-1 infection can alter lipid profiles, yet no research has examined lipid indices and liver function tests in these patients in the long term. METHODS: This data is part of the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study. A total of 1116 participants were randomly selected, including 837 healthy individuals and 279 HTLV-1-infected patients. Following a 10-year follow-up period, Serum levels of liver enzymes were measured. Lipid indices such as the Atherogenic Index of Plasma (AIP), Body Adiposity Index (BAC), Castelli risk index (CRI-I, CRI-II), Lipid Accumulation Product (LAP), Visceral Adiposity Index (VAI), Triglyceride-glucose index (TyG), and Triglyceride and HDL-C Ratio (THR) were calculated. RESULTS: Multivariable-adjusted regression analysis demonstrated a significant coefficient for the Visceral Adiposity Index (VAI) in HTLV-infected patients compared to healthy controls (B: -0.014, 95% CI: -0.02, 0.00, p = 0.046). However, no significant differences were observed in other lipid indices between HTLV-infected patients and healthy individuals. Regarding liver enzymes, significant variations were noted in HTLV-infected patients compared to healthy controls: Aspartate Aminotransferase (AST) (B: 2.978, 95% CI: 1.34, 4.61, p < 0.001), Alanine Aminotransferase (ALT) (B: 3.687, 95% CI: 1.59, 5.78, p = 0.001), Alkaline Phosphatase (ALP) (B: 18.232, 95% CI: 6.81, 29.65, p = 0.002), and Gamma-Glutamyl Transferase (GGT) (B: 3.714, 95% CI: 0.18, 7.24, p = 0.039). CONCLUSION: Individuals with HTLV-1 infection exhibit reduced VAI but elevated levels of liver enzymes such as AST, ALT, ALP, and GGT, indicating liver damage. These findings emphasize the virus's involvement in liver pathology. Also, HTLV-I is associated with reduced visceral fat tissue.

Dendritic Cells Pulsed with HAM/TSP Exosomes Sensitize CD4 T Cells to Enhance HTLV-1 Infection, Induce Helper T-Cell Polarization, and Decrease Cytotoxic T-Cell Response.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive demyelinating disease of the spinal cord due to chronic inflammation. Hallmarks of disease pathology include dysfunctional anti-viral responses and the infiltration of HTLV-1-infected CD4+ T cells and HTLV-1-specific CD8+ T cells in the central nervous system. HAM/TSP individuals exhibit CD4+ and CD8+ T cells with elevated co-expression of multiple inhibitory immune checkpoint proteins (ICPs), but ICP blockade strategies can only partially restore CD8+ T-cell effector function. Exosomes, small extracellular vesicles, can enhance the spread of viral infections and blunt anti-viral responses. Here, we evaluated the impact of exosomes isolated from HTLV-1-infected cells and HAM/TSP patient sera on dendritic cell (DC) and T-cell phenotypes and function. We observed that exosomes derived from HTLV-infected cell lines (OSP2) elicit proinflammatory cytokine responses in DCs, promote helper CD4+ T-cell polarization, and suppress CD8+ T-cell effector function. Furthermore, exosomes from individuals with HAM/TSP stimulate CD4+ T-cell polarization, marked by increased Th1 and regulatory T-cell differentiation. We conclude that exosomes in the setting of HAM/TSP are detrimental to DC and T-cell function and may contribute to the progression of pathology with HTLV-1 infection.

Plasma vitamin D levels are correlated with the pathogenesis of human T-cell leukemia virus type 1-associated diseases.

The active form of vitamin D (VD) exerts hormonal effects by regulating the expression of genes involved in T-cell activity, cell differentiation, and proliferation. Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of life-threatening diseases, adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy (HAM). Among ATL patients, hypercalcemia is one of the most serious complications due to bone resorption. In this study, wild-type mice administered UV-irradiated HTLV-1-infected cells showed up to 47% decrease of plasma VD level compared with untreated mice. To clarify the effect of HTLV-1 on plasma VD level, 315 samples registered in nationwide cohort study on ATL onset were measured. The VD level in HAM (14.98 ± 8.5 ng/mL) was significantly lower than those in asymptomatic carriers and ATL (p < 0.05). Upon comparing the VD levels in ATL stratified by disease subtypes, acute ATL showed a lower level (15.81 ± 12.0 ng/mL) than chronic and smoldering types (p < 0.05). In the longitudinal observation, VD levels were significantly higher in untreated spontaneous remission cases than in ATL progression cases, in which the VD levels decreased approximately 40% after onset. In cases of relapse after transplantation, the plasma VD level dropped to 38.7% of the pre-relapse level, while in cases of complete remission, the VD level increased with improvement of the performance status. Taken together, these results suggest that plasma VD level is a potential indicator for the onset and relapse of HTLV-1-associated diseases.

Peculiar transcriptional reprogramming with functional impairment of dendritic cells upon exposure to transformed HTLV-1-infected cells.

Manipulation of immune cell functions, independently of direct infection of these cells, emerges as a key process in viral pathophysiology. Chronic infection by Human T-cell Leukemia Virus type 1 (HTLV-1) is associated with immune dysfunctions, including misdirected responses of dendritic cells (DCs). Here, we interrogate the ability of transformed HTLV-1-infected T cells to manipulate human DC functions. We show that exposure to transformed HTLV-1-infected T cells induces a biased and peculiar transcriptional signature in monocyte-derived DCs, associated with an inefficient maturation and a poor responsiveness to subsequent stimulation by a TLR4 agonist. This poor responsiveness is also associated with a unique transcriptional landscape characterized by a set of genes whose expression is either conferred, impaired or abolished by HTLV-1 pre-exposure. Induction of this functional impairment requires several hours of coculture with transformed HTLV-1-infected cells, and associated mechanisms driven by viral capture, cell-cell contacts, and soluble mediators. Altogether, this cross-talk between infected T cells and DCs illustrate how HTLV-1 might co-opt communications between cells to induce a unique local tolerogenic immune microenvironment suitable for its own persistence.

Does Antiretroviral Therapy Prevent Human T-Lymphotropic Virus 1 Transmission From a Seropositive Donor to a Kidney Transplant Recipient? A Case Report and Literature Review.

Human T-lymphotropic virus 1 produces a latent infection and disease with poor prognosis. Although its transmission during solid-organ transplant and development of the disease has been described, it is not clear whether antiretroviral treatment could prevent it. We report the first kidney transplant of a donor with human T-lymphotropic virus positivity to a negative recipient who was under antiretroviral treatment without evidence of transmission. We reviewed the literature, which included reports of 55 solid-organ transplant donors with human T-lymphotropic virus positivity to negative recipients, showing high rates of transmission and disease. The benefits of antiretroviral treatment require evaluation in further studies.

Mapping variants in HTLV-1 genome to analyze their impacts on the HAM/TSP development: A systematic review.

The reasons that lead some individuals living with the Human T Lymphotropic Virus 1 (HTLV-1) to develop HAM/TSP are still unclear. To better understand the viral genetic factors that may be associated with the development of HAM/TSP, this study aims to evaluate the impact of HTLV-1 genome mutations on the development of this disease through a systematic review. This review followed the PRISMA guidelines and was registered in the PROSPERO database. The search for articles was performed in PMC, PubMed, Lilacs, SciELO, and Embase databases using the following search descriptors: HTLV-1, HAM/TSP, mutation, polymorphism, genetic variation, and sequenc*. From the 1,929 articles found in the search, 20 were selected according to the pre-defined inclusion and exclusion criteria. A total of 619 HAM/TSP cases were compared with 555 AC controls. The mutations possibly related to the disease progression were detected in hbz (R119Q), tax (A7959V), ORF-I (R88K, P86S, S69G, P45L, L40F, C39R, CR9Y), and gp46 (V247I, N93D, S72G) genetic regions. The data collected and analyzed here indicate that mutations in the HTLV-1 genome could play an important role in the chronic inflammatory state and may be related to the development of HAM/TSP.

Wavelet Collocation Method for HIV-1/HTLV-I Co-Infection Model Using Hermite Polynomial.

In this study, the dynamic behavior of fractional order co-infection model with human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type I (HTLV-I) is analyzed using operational matrix of Hermite wavelet collocation method. Also, the uniqueness and existence of solutions are calculated based on the fixed point hypothesis. For the fractional order co-infection model, its positivity and boundedness are demonstrated. Furthermore, different types of Ulam-Hyres stability are also discussed. The numerical solution of the model are obtained by using the operational matrix of the Hermite wavelet approach. This scheme is used to solve the system of nonlinear equations that are very fruitful and easy to implement. Additionally, the stability analysis of the numerical scheme is explained. The mathematical model taken in this work incorporates the biological characteristics of both HIV-1 and HTLV-I. After that all the equilibrium points of the fractional order co-infection model are found and their existence conditions are explored with the help of the Caputo derivative. The global stability of all equilibrium points of this model are determined with the help of Lyapunov functions and the LaSalle invariance principle. Convergence analysis is also discussed. Hermite wavelet operational matrix methods are more accurate and convergent than other numerical methods. Lastly, variations in model dynamics are found when examining different fractional order values. These findings will be valuable to biologists in the treatment of HIV-1/HTLV-I.

Southern African Origin of HTLV-1 in Romania.

In Europe, most HTLV-1-infected individuals originate from highly endemic regions such as West Indies, sub-Saharan Africa, and South America. The only genuine endemic region for HTLV-1 in Europe is Romania where ATL series have been reported among Romanian patients. Our objective is to better understand the origin of this endemic focus based on a study of the genetic diversity of HTLV-1 in Romanians. DNA was obtained from PBMCs/buffy coats of 11 unrelated HTLV-1-infected individuals of Romanian origin. They include 9 ATL cases and 2 asymptomatic carriers. LTR sequences were obtained for all specimens. Complete genomic HTLV-1 sequences were obtained using four PCR series on 10 specimens. Phylogenetic trees were generated from multiple alignments using HTLV-1 prototypic sequences and the new generated sequences. Most of the complete LTR sequences (756-bp) showed low nucleotide diversity, ranging from 0% to 0.8% difference, and were closely related (less than 0.8% divergence) to the only previously characterized Romanian strain, RKI2. One strain, ROU7, diverged slightly (1.5% on average) from the others. Phylogenetic analyses both on partial LTR and the complete genome demonstrate that the 11 sequences belong to the HTLV-1a cosmopolitan genotype and 10 of them belong to the previously denominated a-TC Mozambique-Southern Africa A subgroup. In this study, we demonstrated that the HTLV-1 present in Romania most probably originated in Southern Africa. As most Romanian HTLV-1 strains are very closely related, we can assume that HTLV-1 has been introduced into the Romanian population recently. Further studies are ongoing to decipher the routes of arrival and dissemination of these HTLV-1 strains, and to date the emergence of this endemic focus in Central Europe.

Novel approaches for HTLV-1 therapy: innovative applications of CRISPR-Cas9.

The human T-cell lymphotropic virus type 1 (HTLV-1) is a single-stranded positive-sense RNA virus that belongs to the Retroviridae family, genus Deltaretro, and infects approximately five to 10 million people worldwide. Although a significant number of individuals living with HTLV-1 remain asymptomatic throughout their lives, some develop one or more severe clinical conditions, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive and debilitating disease, and/or a subtype of non-Hodgkin's lymphoma with a more threatening course known as adult T-cell leukemia/lymphoma (ATLL). Moreover, current therapeutic options are limited and focus primarily on treating symptoms and controlling viral latency. CRISPR-Cas9 gene editing is proposed as a promising tool to address the intricate links associated with HTLV-1. By targeting or silencing key genes during initial infection and dysregulating immune signaling pathways, CRISPR-Cas9 offers potential intervention opportunities. In this review, we address the therapeutic potential of CRISPR-Cas9 gene editing, as well as examine the primary mechanisms involved in editing potential target genes and discuss the existing evidence in the current scientific literature.

A novel high-performance rapid screening test for the detection of total HTLV-I and HTLV-II antibodies in HTLV-I/II infected patients.

Rapid diagnosis of human T-cell lymphotropic virus (HTLV) type-I and -II infections are essential for timely and cost-effective disease interventions. MP Diagnostics ASSURE HTLV-I/II Rapid Test was developed for the rapid detection of anti-HTLV-I/II antibodies in patients' serum, plasma, and whole blood specimens. ASSURE HTLV-I/II Rapid Test employed MP Biomedicals' proprietary HTLV-I/II Trifusion recombinant antigen conjugated with gold nanoparticles and HTLV-I / HTLV-II recombinant antigens immobilized on the nitrocellulose membrane to detect total HTLV-I and HTLV-II antibodies. The overall performance of the ASSURE HTLV-I/II Rapid Test was found to be 99.42% sensitivity (95% Confidence Interval, 98.32-99.88%) and 100% specificity (95% Confidence Interval, 99.58-100.00%) in the tested clinical samples, including a total of 518 HTLV-I/II positive specimens (396 HTLV-I infection, 97 HTLV-II infection and 25 HTLV-I/II dual infection) and 872 HTLV negative clinical specimens consisting of 691 healthy donor samples, 116 potentially cross-reactive samples, and 65 samples with interfering substances. The ASSURE HTLV-I/II Rapid Test can effectively be deployed as a screening tool in any prevalence studies, blood banks or organ transplant centres.

Role of Interleukin-17 cytokine family in human T-cell lymphotropic virus type 1 (HTLV-1) infection and associated diseases.

BACKGROUND: Human T-lymphotropic virus (HTLV-1) is a neglected virus with worldwide distribution of over 10 million people and is the cause of two main associated diseases Adult T cell Leukemia-Lymphoma (ATLL), and HTLV-1-associated Myelopathy/Tropical Spastic paraparesis (HAM/TSP). The IL-17 cytokine family plays a crucial role in the host immunity against HTLV-1 and the development of associated disease. A systematic review was conducted to analyze all research reporting on the levels or expression of the IL-17 HTLV-1 infection and associated diseases. METHODS: The literature search was conducted in electronic databases including PubMed/Medline and Web of Sciences until January 31st, 2024, followed by the PRISMA guidelines. RESULTS: Our search revealed 20 eligible articles to be included in our study. The total number of cases studied was 1420, of which 386 were carriers without any symptoms, and were 176 ATLL and 237 HAM/TSP. The IL-17 cytokine family production or mRNA expression was higher in HAM/TSP patients but showed a trend toward reduction in the case of ATLL. CONCLUSIONS: Our results showed that while The IL-17 cytokine family plays a significant role in the immunopathogenesis of disease and clinical status of patients with inflammatory disorders such as HAM/TSP, IL-17 production is diminished and the RORC/IL-17 signaling pathway is downregulated during ATLL. Our data suggest that boosting the RORC/IL-17 signaling pathway in ATLL and using anti-IL-17 agents in HAM/TSP and other HTLV-related inflammatory conditions might benefit patients and improve their outcomes.

Effects of HTLV-1 on leukocyte trafficking and migration in ACs compared to healthy individuals.

Human T-lymphotropic virus type 1 (HTLV-1) is a RNA virus belonging to Retroviridae family and is associated with the development of various diseases, including adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Aside from HAM/TSP, HTLV-1 has been implicated in the development of several disorders that mimic auto-inflammation. T-cell migration is important topic in the context of HTLV-1 associated diseases progression. The primary objective of this case-control study was to assess the relationship between increased mRNA expression in virus migration following HTLV-1 infection. PBMCs from 20 asymptomatic patients and 20 healthy subjects were analyzed using real-time PCR to measure mRNA expression of LFA1, MLCK, RAC1, RAPL, ROCK1, VAV1 and CXCR4. Also, mRNA expression of Tax and HBZ were evaluated. Mean expression of Tax and HBZ in ACs (asymptomatic carriers) was 0.7218 and 0.6517 respectively. The results revealed a noteworthy upregulation of these genes involved in T-cell migration among ACs patients in comparison to healthy individuals. Considering the pivotal role of gene expression alterations associated with the progression into two major diseases (ATLL or HAM/TSP), analyzing the expression of these genes in the ACs group can offer probable potential diagnostic markers and aid in monitoring the condition of ACs.

Molecular and Phylogenetic Evidence of Interfamilial Transmission of HTLV-1 in the Afro-Descendant Community of São José de Icatú in the Brazilian Amazon.

This study aimed to describe the prevalence of HTLV-1/2 in quilombola communities in the state of Pará and investigate the possible sociodemographic risk factors associated with the infection, as well as to trace the occurrence of the familial transmission of the virus. A total of 310 individuals living in eight quilombos located in the state of Pará (northern Brazil) were investigated for the presence of anti-HTLV-1/2 antibodies using an enzyme-linked immunosorbent assay (ELISA), and positive samples were confirmed using Western blot and/or real-time quantitative polymerase chain reaction (qPCR). Participants answered a questionnaire about sociodemographic aspects and risk factors for infection. Anti-HTLV-1/2 antibodies were detected in two individuals (one man and one woman), for an overall seroprevalence of 0.65%. Both individuals belonged to the community of São José de Icatú. The search for intrafamilial infection identified two other infected women, which increased the general prevalence of HTLV-1 among the Icatú to 6.25% (4/64). Western blot and qPCR confirmed their HTLV-1 infection, and phylogenetic analysis demonstrated that the isolates were of the cosmopolitan subtype and transcontinental subgroup. Epidemiological investigation of the cases revealed that the three women, at some point in their lives, had a relationship with the infected male individual. HTLV-1 is transmitted silently between individuals in the community of São José de Icatú with a present or past family relationship, stressing the need for screening and laboratory diagnosis to prevent further dissemination of the virus and surveillance of disease emergence.