Human T-cell Lymphotropic Virus Research Articles

Correlation Between TWEAK Serum Level and HTLV-1 Proviral Load in HAM/TSP.

Human T-cell lymphotropic virus type-I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the main neurological manifestation of HTLV-I, is a chronic inflammatory disease. Viral-host interaction and host genetics are two important contributors to the development of the HAM/TSP. This study was conducted to measure the serum level of tumor necrosis factor-alpha-like weak inducer of apoptosis (TWEAK) by ELISA method in three groups of participants including 34 HAM/TSP patients (HAM/TSP), 35 asymptomatic HTLV-1 carriers (ACs), and 20 healthy controls (HCs). Also, the titer of the proviral load in two groups of HAM/TSP and ACs was assessed by the real-time polymerase chain reaction (PCR). The statistical results showed that, there is no significant difference between the three groups in TWEAK cytokine level (p = 0.667). Also, there was no significant difference in proviral load titer between groups of HAM/TSP and ACs (p = 0.08). Furthermore, no significant difference was observed between proviral load and TWEAK cytokine concentration between groups of HAM/TSP and ACs. Our findings showed that despite the inflammatory nature of HAM/TSP disease, the expression level of TWEAK in HAM/TSP patients is not significantly different from the groups of ACs and HCs. Therefore, the involvement of other factors in causing HAM/TSP is not unexpected.

A novel hybrid method with convergence analysis for approximation of HTLV-I dynamics model

This paper presents a novel numerical approach for approximating the solution of the model describing the infection of CD4+T\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$CD4^+T$$\\end{document}-cells by the human T-cell lymphotropic virus I (HTLV-I).The proposed method utilizes the operational matrix along with spectral method to convert the fractional model into a system of nonlinear algebraic equations. The Levenberg-Marquardt algorithm efficiently solves these equations. The study includes theoretical convergence analysis and error bounds to establish the validity of the proposed method. Through several test problems, we demonstrate the effectiveness and accuracy of the approach. We compare its performance and reliability to other existing methods in the literature. The results indicate that the proposed method is a reliable and efficient approach for solving the model.

Human T-cell lymphotropic virus: knowledge of academics from a higher education institution

Objective: To estimate the knowledge of nursing students from two higher education institutions in relation to Human T-cell Lymphotropic Virus. Materials and Methods: This is a quantitative descriptive and cross-sectional study, conducted with nursing students from a higher education institution in Minas Gerais, in October 2023. In this work, it was decided to develop a data collection instrument, applied through an online questionnaire made available by the Google Forms platform. Results: A total of 91 questionnaires were received, of which 81 were validated, and it was observed that 70% of the students stated that they had no knowledge about this virus. However, in the specific questions about the Human T-Cell Lymphotropic Virus, the average rate of correct answers of 58.91% was tabulated and calculated. Conclusion: Thus, since these are future health professionals, this percentage is considered below what is necessary, so it is essential to have a greater involvement of this group with the theme, in order to improve the management of cases, avoiding greater transmissibility of the virus.

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

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. 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. 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. 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. 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.

Structure Of The Single Health System For Diagnosis Of Htlv-1/2 In The Northern Region Of Tocantins

Background: The Human T-cell Lymphotropic Virus (HTLV), the first human retrovirus discovered, is associated with oncogenesis and is subdivided into several groups, with types 1 and 2 being the most prevalent and clinically relevant. Its main forms of transmission include unprotected sexual intercourse, blood transfusions, tissue and organ transplants, as well as vertical transmission (mother to newborn). In Brazil, mandatory testing for HTLV was implemented in the 1990s for blood donations and transplants, and expanded in 2024 by Ordinance No. 3,148 of the Ministry of Health, which includes testing during prenatal care. Objective: This study aimed to evaluate the structure of the Unified Health System (SUS) in the municipalities of the far north of Tocantins for the diagnosis of HTLV-1/2. Methodology: This is a qualitative study, in which semi-structured questionnaires were applied to Primary Care professionals and municipal health managers. Results: The results indicated significant deficiencies in knowledge of national protocols and the absence of a structured municipal flow for testing. Conclusion: It can be concluded that the health structure of the municipalities evaluated is insufficient for the effective diagnosis of HTLV-1/2

267 - Darifenacin versus Parasacral Transcutaneous Electrical Nerve Stimulation for Overactive Bladder Syndrome in Patients Infected With Human T-Cell Lymphotropic Virus 1 – Preliminary Results of a Randomized Clinical Trial

267 - Darifenacin versus Parasacral Transcutaneous Electrical Nerve Stimulation for Overactive Bladder Syndrome in Patients Infected With Human T-Cell Lymphotropic Virus 1 – Preliminary Results of a Randomized Clinical Trial

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.

Immunophenotypic, genetic, and clinical characterization of adult T-cell leukemia/lymphoma: A single tertiary care center experience in the United States.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). Its most common immunophenotype is CD4+/CD7-/CD25+, although unusual immunophenotypes can occur and may lead to misdiagnosis. The immunophenotypes, cytogenetics, molecular features, clinical presentations, treatment, and prognosis of 131 patients with ATLL were retrospectively studied in a large tertiary medical center in the United States. All cases showed loss of CD7 expression. While 82.4% of cases demonstrated CD4+, 17.6% exhibited unusual phenotypes, including CD4+/CD8+ (6.9%), CD4-/CD8- (2.3%), CD5- (3.1%), CD2-, and CD3-. The most common cytogenetics abnormalities included polysomy 3 (34.6%), translocation 1 (23.1%), and abnormalities found on chromosome 11 (30.8%) and chromosome 14 (26.9%). The common gene mutations identified by the next-generation sequencing study were TP53 (16.7%), TBL1XR1 (16.7%), EP300 (14.3%), and NOTCH1 (14.3%). TBL1XR1 mutation is associated with genetic instabilities. There was no significant difference between the clinical presentations of these 2 groups. Adult T-cell leukemia/lymphoma exhibits versatile immunophenotypic, cytogenetic, and molecular features. Simultaneous involvement of blood, lymph nodes, and other organs, along with hypercalcemia in a patient from an endemic area, necessitates HTLV-1 testing to avoid underdiagnosis of this dismal disease that might need aggressive chemotherapy followed by bone marrow transplant.

Urodynamic findings and vibegron effects on neurogenic lower urinary tract dysfunction caused by human T-cell leukemia virus type I-associated myelopathy/tropical spastic paraparesis.

Human T-cell lymphotropic virus type 1 infection can cause HTLV-1-associated myelopathy/tropical spastic paraparesis, characterized by spastic paralysis of both lower limbs. More than 90% of HAM/TSP patients show lower urinary tract symptoms and dysfunction. A 27-year-old woman diagnosed with HAM/TSP presented with overactive bladder. A urodynamic study revealed detrusor overactivity. OAB remained despite improvements in spastic paralysis of the lower limbs after starting prednisolone. The addition of solifenacin likewise failed to improve OAB or DO in this patient. Switching from solifenacin to vibegron improved OAB symptoms. In patients for whom OAB and DO do not improve with steroid treatment and solifenacin, treatment with vibegron may improve OAB symptoms.

A Systematical Review on ART Use in HTLV Infection: Clinical, Virological, and Immunological Outcomes.

Human T-cell lymphotropic virus (HTLV) infection affects over ten million people worldwide, but there is no effective treatment so far. This review describes the virological, immunological, and clinical outcomes of antiretroviral therapy (ART) in people with HTLV infection. This systematic review followed PRISMA reporting guidelines and was registered in PROSPERO: CRD42022350076. The Newcastle-Ottawa Scale, adapted for cross-sectional studies, and Rob-2 were used to assess the methodological quality of these studies. Systematic searches were conducted in the Medline (PubMed), Scopus (Elsevier), Cochrane Library, and Web of Science (Clarivate Analytics) databases. We retrieved data from eight methodologically diverse articles on treatment of patients infected by HTLV-1 or HTLV-2 alone, or coinfected by HIV-1, who received Raltegravir, Tenofovir, Lamivudine, or Zidovudine. The proviral load decreased in three out of seven studies over 4 to 48 weeks of antiretroviral use. Cellular immune response (CD4, CD8, CD25, CD69, and CD71 cells) was evaluated in six studies. While no significant clinical improvement was observed, all studies reported clinical stability during treatment. Despite the demonstrated antiviral activity of ART, in vitro, clinical improvement was not proven. Most studies showed disease stability during ART use, suggesting potential clinical benefits. There is a need of larger, well-controlled trials to define the role of ART in the treatment of HTLV infection.

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.

Association between HTLV-1/2 infection and COVID-19 severity in a migrant Shipibo-Konibo population in Lima, Peru.

The migrant community of the Shipibo-Konibo indigenous people in Lima, Peru were extremely vulnerable during the COVID-19 pandemic. Additionally, infection with human T-cell lymphotropic virus type 1 and 2 (HTLV-1/2) is endemic in this population causing immunosuppression. The aim of the study was to describe the association between HTLV-1/2 infection and the clinical severity of COVID-19. This was a cross-sectional descriptive study involving a survey of adult Shipibo-Konibo indigenous migrants residing in Cantagallo-Rímac who were identified as suspected or confirmed cases of COVID-19. Blood samples were collected for SARS-CoV-2 antibody and HTLV-1/2 ELISA testing. A confirmatory Western Blot test was performed for those with a positive ELISA test. A total of 182 individuals were surveyed and sampled. No significant association was found between HTLV-1/2 infection and the clinical severity of COVID-19. The prevalence of HTLV-1/2 was 8.8% (95%CI: 5.0-14.1) with Western Blot. Age was the only statistically significant risk factor for developing a more severe form of COVID-19 (OR: 1.03; 95%CI: 1.00-1.06; p = 0.032). There was no association found between HTLV-1/2 infection and the clinical severity of COVID-19. The prevalence of HTLV-1/2 infection in the Shipibo-Konibo population is high and warrants continuous monitoring in the advent of other infectious disease outbreaks and the development of HTLV-associated comorbidities.

Neurological Manifestations and Risk Factors of HTLV-1 Infection in the Middle East Region and Iran: A Comprehensive Review of 137 Articles of the Last 23 Years

Background & Objectives: The Human T-cell lymphotropic virus type 1 (HTLV-1) retrovirus is prevalent in some regions, such as Iran. This comprehensive literature review explores the symptoms and risk factors associated with HTLV-1 infection Middle East Region and Iran. Materials & Methods: This narrative review used PubMed, Scopus, Embase, ScienceDirect, and Google Scholar as searching engines using terms HTLV-1, neurological disorders, pathogenesis, transmission, diagnosis, treatment, and epidemiology for articles published between 2000 and 2023. In total, 137 articles were eligible. Results: Breastfeeding, unsafe sexual contact, and contaminated blood products are main HTLV -1 transmission routes. Brazil, Ecuador, and the Dominican Republic are countries with a high percentage of HTLV-1 infection, with estimates ranging from 1% to 13.9% in Brazil, up to 57% in Ecuador, and 1% to 5% in the Dominican Republic and it is endemic in Iran, Japan, the Caribbean, South America, and Africa. While numerous patients are asymptomatic, the virus can cause HTLV1 -associated myelopathy/tropical spastic paraparesis (HAM/TSP) and peripheral neuropathy. Tax viral proteins cause nervous system inflammation and HAM/TSP. MRI (magnetic resonance imaging) may decipher spinal cord shrinkage and white matter lesions in affected patients. Immunodeficiency conditions, blood transfusion, and risky sexual behavior increase infection rate. The neurological symptoms are initiated with sensory -motor impairments. The main symptoms are limb weakness, bladder/bowel dysfunction, and cognitive impairment. Conclusion: HTLV-1 infection is highly prevalent in Japan, Africa, the Caribbean, Central and South America, and Iran (especially in northeastern regions like Neyshabur). By understanding the pathogenesis and epidemiology of HTLV-1, proper strategies and targeted treatments can be developed for associated disorders like HAM/TSP. International collaboration is essential in addressing health concerns related to HTLV -1 infection.

Human T-cell lymphotropic virus screening in France: Missed opportunities? A retrospective multicenter study of serological testing in hospital laboratories

ObjectivesHuman T-lymphotropic virus 1 infection is endemic in the French Antilles, French Guiana, and sub-Saharan Africa, the origin of many immigrants currently living in France. There are no national screening recommendations outside of the regulatory obligations concerning donations of blood, tissue, gametes, or milk to a lactarium. This study aimed to investigate the screening and diagnostic practices for this infection in France. MethodsSerological statistics for regulatory, antenatal, sexually transmitted infections (for CeGIDDs (Centre Gratuit d'Information, de Dépistage et de Diagnostic des Infections Sexuellement Transmissibles), which are public sexual health clinics), accidental exposure to blood screenings, and diagnosis since January 1, 2018 were collected from 23 hospital laboratories (two in the French Antilles, 21 in mainland France) associated with 55 hospitals and 22 maternity units. ResultsA total absence of antenatal screening was reported by 75% of the laboratories associated with maternity units in mainland France. All the laboratories in mainland France reported an absence of screening in the accidental exposure to blood context, as did all the laboratories in mainland France associated with a CeGIDD in the context of sexually transmitted infection screening. Conversely, screening in accordance with the existing regulations was generally systematically carried out. The most frequently reported diagnostic contexts were hematology and neurology. ConclusionsThis study reveals an underscreening of human T-lymphotropic virus 1 in the hospital laboratories of mainland France.

Cell Culture Evaluation Hints Widely Available HIV Drugs Are Primed for Success if Repurposed for HTLV-1 Prevention.

With an estimated 10 million people infected, the deltaretrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the second most prevalent pathogenic retrovirus in humans after HIV-1. Like HIV-1, HTLV-1 overwhelmingly persists in a host via a reservoir of latently infected CD4+ T cells. Although most patients are asymptomatic, HTLV-1-associated pathologies are often debilitating and include adult T-cell leukaemia/lymphoma (ATLL), which presents in mature adulthood and is associated with poor prognosis with short overall survival despite treatment. Curiously, the strongest indicator for the development of ATLL is the acquisition of HTLV-1 through breastfeeding. There are no therapeutic or preventative regimens for HTLV-1. However, antiretrovirals (ARVs), which target the essential retrovirus enzymes, have been developed for and transformed HIV therapy. As the architectures of retroviral enzyme active sites are highly conserved, some HIV-specific compounds are active against HTLV-1. Here, we expand on our work, which showed that integrase strand transfer inhibitors (INSTIs) and some nucleoside reverse transcriptase inhibitors (NRTIs) block HTLV-1 transmission in cell culture. Specifically, we find that dolutegravir, the INSTI currently recommended as the basis of all new combination antiretroviral therapy prescriptions, and the latest prodrug formula of the NRTI tenofovir, tenofovir alafenamide, also potently inhibit HTLV-1 infection. Our results, if replicated in a clinical setting, could see transmission rates of HTLV-1 and future caseloads of HTLV-1-associated pathologies like ATLL dramatically cut via the simple repurposing of already widely available HIV pills in HTLV-1 endemic areas. Considering our findings with the old medical saying "it is better to prevent than cure", we highly recommend the inclusion of INSTIs and tenofovir prodrugs in upcoming HTLV-1 clinical trials as potential prophylactics.

Clinical Features and Survival Outcome in Aggressive-Type Adult T-Cell Leukemia/Lymphoma Patients: Real-Life Experience of a Single Center from an HTLV-1 Endemic Country.

Background and Objectives: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoproliferative disease associated with the human T-cell lymphotropic virus type I (HTLV-1). ATLL is a rare disease, found more frequently in HTLV-1-endemic areas, Romania being one of them. Despite treatment advances, the prognosis remains dismal. We aimed to describe the clinical, biological, and survival outcome features of Romanian patients with aggressive-type ATLL. Materials and Methods: We report the data of a prospective, observational, and unicentric study of all 20 patients diagnosed with lymphoma and acute types of ATLL at our center over the past 12 years. Data were collected from the patients' medical records. Results: Lymphoma-type ATLL (60%) was more common than acute-type ATLL (40%). Median age at diagnosis was 40.5 years, and most patients were female. Laboratory data revealed significant differences between acute and lymphoma-type ATLL, namely, higher leukocyte (p = 0.02) and lymphocyte counts (p = 0.02) and higher levels of corrected calcium (p = 0.001) in acute-type ATLL. All patients received chemotherapy, and only two underwent allogeneic stem cell transplantation. Only six patients obtained a complete or partial response to chemotherapy, mostly the lymphoma-type ones. The median survival for all patients was 6.37 months, with higher survival in the lymphoma-type ATLL (8.16 months) than in the acute-type (3.60 months). Normal calcium levels (p = 0.011), uric acid (p = 0.005), BUN score (p = 0.000), JCOG-PI moderate risk (p = 0.038), and obtaining complete or partial response (p = 0.037) were associated with higher survival. Conclusion: Aggressive-type ATLL among Romanian patients presents distinct characteristics, including younger age at diagnosis, female predominance, and higher incidence of lymphoma-type ATLL compared to currently reported data. Survival remains very low, with all subtypes experiencing a median survival of less than one year.

Prevalence of human T-cell lymphotropic virus-1/2 in Canada over 33years: A unique contribution of blood donors to public health surveillance.

Estimate HTLV-1/2 (human T-cell lymphotropic viruses)prevalence in Canadian blood donors and the association of demographic variables with infection and their corresponding risk factors. First-time blood donors in all Canadian provinces (except Quebec) from 1990 to 2022 were included. Blood samples were tested for HTLV-1/2 by enzyme-linked immunoassay, confirmed by Western blot. Multivariable logistic regression with year, age group, sex, region, neighbourhood material deprivation, and ethnocultural composition indices predicted HTLV-1/2. Since 2005, all HTLV-1/2-positive donors (cases) were invited to participate in a risk factor interview, and 4 non-positive donors (controls per case) were matched for age, sex, and region. Case-control predictors of HTLV-1/2 were analyzed using logistic regression. There were 3,085,554 first-time donors from 1990 to 2022. HTLV-1/2 prevalence remained low (12 per 100,000 in 2022, 95% CI 6.4-23.5). The odds ratios predicting HTLV-1/2 were higher in females (2.0, 95% CI 1.5-2.6), older age groups (50 + ; 6.3, 95% CI 4.3-9.2), British Columbia and Ontario, thosematerially deprived (1.9, 95% CI 1.2-2.9), and those inethnocultural neighbourhoods (7.5, 95% CI 3.2-17.3). Most HTLV-1/2 in Ontario was HTLV-1, whereas in British Columbia half were HTLV-2. Forty-three of 149 (28.8%) cases and 172 of 413 (41.6%) controlscompleted an interview. The strongest predictor of HTLV-1/2 in case-control analysis was birth in a high-prevalence country (OR 39.8, 95% CI 7.8-204.3) but about 50% of HTLV-1 and 90% of HTLV-2 were Canadian-born. HTLV-1/2 prevalence is low in blood donors. High-prevalence country of birth accounts for about half of HTLV-1; HTLV-2 positives are usually Canadian-born. HTLV-1/2 transmission likely occurs overseas and within Canada.

Human T-cell lymphotropic virus type 1 (HTLV-1) grip on T-cells: investigating the viral tapestry of activation

IntroductionHuman T-cell Lymphotropic virus type 1 (HTLV-1) belongs to retroviridae which is connected to two major diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and Adult T-cell leukemia/lymphoma (ATLL). This study aims to investigate the mRNA expressions of key proteins correlated to T-cell activation in asymptomatic carriers (ACs) HTLV-1 infected patients, shedding light on early molecular events and T-cell activation following HTLV-1 infection.Material and MethodsThe study involved 40 participants, including 20 ACs and 20 healthy subjects. Blood samples were collected, ELISA assessment for screening and confirmation with PCR for Trans-activating transcriptional regulatory protein (Tax) and HTLV-1 basic leucine zipper factor (HBZ) of the HTLV-1 were done. mRNA expressions of C-terminal Src kinase (CSK), Glycogen Synthase Kinase-3 Beta (GSK3β), Mitogen-Activated Protein Kinase 14 (MAP3K14 or NIK), Phospholipase C Gamma-1 (PLCG1), Protein Tyrosine Phosphatase non-Receptor Type 6 (PTPN6) and Mitogen-Activated Protein Kinase Kinase Kinase-7 (SLP-76) and Mitogen-Activated Protein Kinase14 (MAP3K7 or TAK1) were assayed using RT-qPCR. Statistical analyses were performed using PRISM and SPSS software.ResultsWhile there were no significant upregulation in CSK and PTPN6 in ACs compared to healthy individuals, expression levels of GSK3β, MAP3K14, PLCG1, SLP-76, and TAK1 were significantly higher in ACs compared to healthy subjects which directly contributes to T-cell activation in the HTLV-1 ACs.ConclusionHTLV-1 infection induces differential mRNA expressions in key proteins associated with T-cell activation. mRNAs related to T-cell activation showed significant upregulation compared to PTPN6 and CSK which contributed to T-cell regulation. Understanding these early molecular events in ACs may provide potential markers for disease progression and identify therapeutic targets for controlling viral replication and mitigating associated diseases. The study contributes novel insights to the limited literature on T-cell activation and HTLV-1 pathogenesis.

Determining optimal surveillance techniques for the microbial community on human skin using RNAseq data analysis

Background: The largest organ in the human body, the skin, serves as a physical barrier to the outside world. It also houses millions of bacteria, viruses, and fungi that protect us against invading pathogens or result in altered physiology and disease. These microorganisms can contribute to normal skin health or predispose individuals to pathogenic disorders. Surveillance and observation of the microbiome can give insight into identifying common taxa that compose our skin and indications of new or changing pathogens. However, to do this effciently, it is important to understand what can be detected from skin samples and the differences we may see using various collection methods. Methods: We used publicly available NCBI SRA RNAseq bioprojects that queried “skin,” processing 132 bioprojects with 8,274 samples. Using FastQC, Salmon, KRAKEN2, and MiCXR/Immunarch, we aimed to analyze the quality, human gene transcripts, infections, and B/T- cell responses, respectively. We aimed to identify what skin sampling method provides the best data on the skin microbiome, human gene mapping, and B/T-cell immune repertoire. This project is based on observational methods, not a specific hypothesis. Results: From the KRAKEN2 data, there were 14,383 viruses and 14,691 bacteria assessed through all “skin” BioProjects. From the extensive data pool, we identified unique BioProject signatures for protest (Leishmania), bacteria (Mycoplasma), and viruses (HSV1 dose dependencies, HPV in human warts, Chinese transmitted tick viruses, Human T-cell lymphotropic virus, and the first-ever human case of equine infectious anemia virus). The use of read mapping and coverage is critical to confirming the presence of foreign species, noted through the observation of T4 DNA ligase RNA presence prior to 2018 RNA sequencing. Once pathogens were detected, cellular response mapping was developed, yielding insights into the pathophysiology of multiple viral infections of the skin and sex differences. Conclusion: Detecting a wide variety of microorganisms on the skin can give insight into dermatological pathologies and skin physiology. Using the publicly available skin datasets, we see many unique stories of microorganisms in the skin. This big data mapping strategy highlights the importance of broad observational mapping, possible with cutting-edge sequencing tools. This work was supported by the MI-SAPPHIRE program of MDHHS and the CDC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact and economic analysis of human T-cell lymphotropic virus type 1 (HTLV-1)-targeted antenatal screening, England and Wales, 2021.

BackgroundHuman T-cell lymphotropic virus type 1 (HTLV-1) is a neglected virus that can cause severe disease and be transmitted from mother to child through breastfeeding. Avoidance of breastfeeding prevents 80% of vertical transmission. The United Kingdom (UK) is currently assessing whether HTLV-1-targeted antenatal screening should be implemented.AimWe aimed to assess the impact and cost-effectiveness of a targeted programme to prevent HTLV-1 vertical transmission in England and Wales.MethodsWe estimated the number of pregnant women who have high risk of HTLV-1 infection based on their or their partner's country of birth. With data from 2021, we used a mathematical model to assess cost-effectiveness of HTLV-1 antenatal screening. We also estimated the annual number of infant infections and the number that could be prevented with screening and intervention.ResultsWe estimate that ca 99,000 pregnant women in England and Wales have high risk of HTLV-1 infection. In the absence of screening, 74 (range: 25-211) HTLV-1 infections in infants would be expected to occur every year in England and Wales. Implementation of targeted screening would prevent 58 (range: 19-164) infant infections annually. The intervention is effective (incremental 0.00333 quality-adjusted life years (QALY)) and cost-saving (GBP -57.56 (EUR -66.85)).ConclusionOur findings support implementation of HTLV-1 targeted antenatal screening to reduce vertical transmission from mothers to infants in the UK.