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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. [ABSTRACT FROM AUTHOR]

Context: The most reported viral co‐infections in leprosy are human immunodeficiency virus (HIV), human T‐cell lymphotropic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV), and SARS‐CoV‐2. In co‐infections, the burden of an agent can be increased or decreased by the presence of others. To address this issue, we need to fully understand their prevalence, risk factors, immunology, clinical manifestations, and treatment. The purpose of this scoping review is to describe the clinical and epidemiological characteristics of the most reported viral co‐infections in leprosy to inform clinicians and guide future research. Methods: The authors conducted a literature search of five databases for articles on each of the aforementioned co‐infections published prior to October 2022. Two independent reviewers conducted the selection process and identified 53 papers meeting the study inclusion criteria. The data extraction process and evidence synthesis were conducted by one reviewer and double‐checked by a second one, consistent with best practice recommendations for scoping reviews. Results: For all assessed viruses, most studies reported prevalence rates in leprosy patients higher than the general population. Studies found that HTLV, HBV, and HCV chronic infections were highest in multibacillary leprosy, whereas HIV was mostly found in paucibacillary leprosy, and SARS‐Cov‐2 affected leprosy subtypes equally. Overall, co‐infections were also associated with higher rates of leprosy reactions, except for COVID‐19. Forty‐six percent of the studies discussed issues related to treatment, which led to favorable outcomes for the most part. Conclusions: This review summarizes the existing literature on viral co‐infections in leprosy patients, generating valuable insights and recommending areas for future research. [ABSTRACT FROM AUTHOR]

In several publications, the dynamical system of HIV and HTLV mono-infections taking into account diffusion, as well as latently infected cells in cellular transmission has been mathematically analyzed. However, no work has been conducted on HTLV/HIV co-infection dynamics taking both factors into consideration. In this paper, a partial differential equations (PDEs) model of HTLV/HIV dual infection was developed and analyzed, considering the cells' and viruses' spatial mobility. CD 4 + T cells are the primary target of both HTLV and HIV. For HIV, there are three routes of transmission: free-to-cell (FTC), latent infected-to-cell (ITC), and active ITC. In contrast, HTLV transmits horizontally through ITC contact and vertically through the mitosis of active HTLV-infected cells. In the beginning, the well-posedness of the model was investigated by proving the existence of global solutions and the boundedness. Eight threshold parameters that determine the existence and stability of the eight equilibria of the model were obtained. Lyapunov functions together with the Lyapunov–LaSalle asymptotic stability theorem were used to investigate the global stability of all equilibria. Finally, the theoretical results were verified utilizing numerical simulations. [ABSTRACT FROM AUTHOR]

The aim of the present paper is to formulate two new mathematical models to describe the co-dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human T-cell lymphotropic virus type-I (HTLV-I) in a host. The models characterizes the interplaying between seven compartments, uninfected ECs, latently SARS-CoV-2-infected ECs, actively SARS-CoV-2-infected ECs, free SARS-CoV-2 particles, uninfected CD4 + T cells, latently HTLV-I-infected CD4 + T cells and actively HTLV-I-infected CD4 + T cells. The models incorporate five intracellular time delays: (i) two delays in the formation of latently SARS-CoV-2-infected ECs and latently HTLV-I-infected CD4 + T cells, (ii) two delays in the reactivation of latently SARS-CoV-2-infected ECs and latently HTLV-I-infected CD4 + T cells, and (iii) maturation delay of new SARS-CoV-2 virions. We consider discrete-time delays and distributed-time delays in the first and second models, respectively. We first investigate the properties of the model's solutions, then we calculate all equilibria and study their global stability. The global asymptotic stability is examined by constructing Lyapunov functionals. The analytical findings are supported via numerical simulation. The impact of time delays on the coinfection progression is discussed. We found that, increasing time delays values can have an antiviral treatment-like impact. Our developed coinfection model can contribute to understand the SARS-CoV-2 and HTLV-I co-dynamics and help to select suitable treatment strategies for COVID-19 patients with HTLV-I. [ABSTRACT FROM AUTHOR]

Natural products (NPs) were a rich source of diverse bioactive molecules. Most anti-tumor agents were built on natural scaffolds. Nardostachys jatamansi DC. was an important plant used to process the traditional Chinese herbal medicines "gansong". Pancreatic cancer was the fourth most common cause of cancer-related death in the world. Hence, there was an urgent need to develop novel agents for the treatment of pancreatic cancer. In this paper, nardoguaianone L (G-6) is isolated from N. jatamansi, which inhibited SW1990 cells colony formation and cell migration, and induced cell apoptosis. Furthermore, we analyzed the differential expression proteins after treatment with G-6 in SW1990 cells by using iTRAQ/TMT-based quantitative proteomics technology, and the results showed that G-6 regulated 143 proteins' differential expression by GO annotation, including biological process, cellular component, and molecular function. Meanwhile, KEGG enrichment found that with Human T-cell leukemia virus, one infection was the most highly enhanced pathway. Furthermore, the MET/PTEN/TGF-β pathway was identified as a significant pathway that had important biological functions, including cell migration and motility by PPI network analysis in SW1990 cells. Taken together, our study found that G-6 is a potential anti-pancreatic cancer agent with regulation of MET/PTEN/TGF-β pathway. [ABSTRACT FROM AUTHOR]

Background: Adult T-cell leukemia/lymphoma (ATLL), a peripheral T-cell leukemia/lymphoma associated with the human T-cell lymphotropic virus type-1 (HTLV-1), has been classified following the clinical forms defined by Shimoyama in 1991. A suggestion to modify Shimoyama's classification was proposed in 2007 to differentiate within the smoldering patients those who presented nodules or tumors in the skin without lung involvement, which was named the primary cutaneous tumoral (PCT) form of ATLL. In the present study, according to their clinicopathological characteristics, we estimated the mortality rates of 143 ATLL patients from Bahia, Brazil. We also evaluated the importance of classifying PCT/ATLL separately from the smoldering type on disease prognosis. Methodology/Principal findings: Diagnosis of ATLL was established based on a positive serology for HTLV-1, histopathological and/or cytological diagnosis of peripheral T-cell leukemia/lymphoma. Patients were clinically grouped according to Shimoyama's classification, considering PCT variants separately from the smoldering cases. Bivariate and multivariable survival analyses were applied to identify factors associated with disease prognosis. Significant differences in the median survival time were observed between the clinical types, with the smoldering type presenting the longest median survival (109 months) compared to the other forms (<50 months); the median survival for PCT/ATLL was 20 months. Multivariable analysis confirmed that ATLL clinical types were associated with survival, with a better prognosis for patients with the smoldering and chronic types. Furthermore, skin involvement was related to a worse outcome in the multivariable analysis, regardless of the clinical form and presence of lymphadenopathy. Conclusions/Significance: Our results reinforce the importance of considering the PCT/ATLL separately from the smoldering type when classifying ATLL to better define prognosis and treatment, given the significant difference in the survival of patients between the smoldering form and PCT/ATLL. Skin involvement should also be considered an independent prognostic factor in patients with ATLL. Author summary: The human T-cell lymphotropic virus type-1 (HTLV-1) may cause serious diseases, such as adult T-cell leukemia/lymphoma (ATLL), which can manifest itself in different clinical forms. In this paper, we investigated the survival of 143 Brazilian ATLL patients, according to the clinical form and other clinicopathological characteristics using bivariate and multivariable analyses. The original clinical classification of ATLL was employed; however, we considered the primary cutaneous tumoral (PCT) ATLL and the smoldering type separately. We found statistically significant differences in the mortality rates by clinical types and highlighted the better prognosis of patients with the smoldering type (mortality rate: 0.6 per 100 person-years) compared to those with PCT (mortality rate: 5.3 per 100 person-years). This finding emphasizes the importance of considering the PCT/ATLL separately from the smoldering type when using the ATLL classification to determine prognosis and treatment. PCT/ATLL should be treated with more aggressive ATLL protocols than the smoldering type without skin nodules or tumors. [ABSTRACT FROM AUTHOR]

HIV and HTLV-I are two retroviruses that infect the CD 4 + T cells. HIV causes acquired immunodeficiency syndrome, while HTLV-I is the causative agent for adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. It is not surprising that a mono-infected patient with one of these viruses can be exposure to co-infect with the other virus since they share the same way of transmissions between individuals, through direct contact with certain contaminated body fluids. Mathematical modeling and analysis of HIV and HTLV-I mono-infections have received considerable attention during the last decades. However, the dynamics of HIV/HTLV-I co-infection has not been formulated. In the present paper, we formulate a new HIV/HTLV-I co-infection model with cytotoxic T lymphocytes (CTLs) immune response. The model describes the interaction between susceptible CD 4 + T cells, HIV-infected cells, Tax-expressing HTLV-infected cells, free HIV particles, HIV-specific CTLs and HTLV-specific CTLs. The HIV can spread by virus-to-cell and cell-to-cell transmissions, while the HTLV-I can only spread via cell-to-cell transmission. The well-posedness of the model is established by showing that the solutions of the model are nonnegative and bounded. We derive the threshold parameters which govern the existence and stability of all equilibria of the model. We prove the global asymptotic stability of all equilibria by utilizing Lyapunov function and applying Lyapunov–LaSalle asymptotic stability theorem. We present numerical simulations to illustrate the effectiveness of our main results. In addition, we discuss the effect of HTLV-I infection on the HIV-infected patients and vice versa. [ABSTRACT FROM AUTHOR]

• A model for HTLV-I infection that includes uninfected & infected CD4+T cells and HTLV-I-specific CD8+T cells. • To better understand the dynamics of HTLV-I infection, we incorporate a CTL immune response delay. • Applying Lyapunov functional procedures to determine global stability by the reproduction numbers R0 and R1. • The model with delay experiences a destabilization of the infected steady state leading to Hopf bifurcation and periodic solutions. • We estimate the length of delay to preserve the stability of bifurcating limit cycle using Nyquist criteria. This paper deals with a four dimensional mathematical model for Human T-cell leukemia virus type-I (HTLV-I) infection that includes delayed CD8+ cytotoxic T-cells (CTLs) immune response. The proposed system has three biologically feasible steady states, namely disease-free steady state, CTL-inactive steady state and an interior steady state. Our theoretical analysis demonstrates that local and global stability analysis are established by the two critical parameters R 0 and R 1 , basic reproduction numbers due to viral infection and due to CTLs immune response, respectively. The disease-free steady state E 0 is globally stable if R 0 ≤ 1 , and the HTLV-I infections are eliminated. The asymptotic-carrier steady state E 1 is globally stable if R 1 ≤ 1 < R 0 , which indicates HTLV-I infection is chronic without persistence of CTLs immune response. The interior steady state E 2 is globally asymptotic stable if R 1 > 1 , which implies that the HTLV-I infection is choric in persistence of CTLs immune response. Due to immune response delay, our proposed model undergoes a destabilization of the interior steady state leading to Hopf bifurcation and periodic oscillations. We estimate the length of time delay that preserve the stability of period-1 limit cycle. We also derived the direction and stability of Hopf bifurcation around the interior steady state by center manifold theory and normal form method. To determine the robustness of the model, we performed normalized forward sensitivity analysis with reference to R 0 and R 1. Our proposed model undergoes Hopf bifurcation with respect to the production rate of uninfected CD4+T cells h , removal rate of virus-specific CTLs d 4 , spontaneous infected CD4+T cell activation d 2 and transmissibility coefficient β. Implications of our numerical illustrations to the pathogenesis of HTLV-I infection and the development of HTLV-I related HAM/TSP are explored. [ABSTRACT FROM AUTHOR]