Lymphotropic Virus Type Research Articles

Prevalence of transfusion-transmitted infections in hospitalized patients before transfusion and volunteer blood donors in Zhejiang Province, China.

ObjectivesTo assess the need for screening of transfusion-transmitted infections (TTIs) in blood products, we assessed TTI seroprevalence in blood donors and hospitalized patients. MethodsWe collected 2760 serum samples from three regions of Hangzhou, Ningbo and Huzhou from April 2021 to March 2022, and they tested by enzyme-linked immunosorbent assay (ELISA) for Hepatitis B surface antigen (HBsAg), Hepatitis C (HCV), Treponema pallidum (TP), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Hepatitis E virus (HEV) and Human T-cell lymphotropic virus type 1/2 (HTLV-1/2) antibody levels. ResultsScreening test results showed that the positive rates for HBsAg, anti-HCV and anti-TP were 3.01 %, 0.39 % and 0.18 %, respectively. The positive rates for CMV IgM and CMV IgG were 0.76 % and 96.96 %, while the positive rates for EB VCA-IgM and EB EA-IgG were 1.88 % and 10.47 %; those for HEV IgM and HEV IgG were 1.16 % and 26.05 %, while the HTLV-1/2 antibody positive rate was 0.04 %. The positive rates for CMV IgG, EB EA-IgG and HEV IgG in hospitalized patients before transfusion were higher than in volunteer blood donors, and the difference was statistically significant (P < 0.05). The overall co-infection rate was 0.29 %. The positive rates for EB VCA-IgM in the males were significantly higher than in females, and EB VCA-IgM and HEV IgG prevalence varied significantly by age. ConclusionOur data demonstrate the risk of TTI exposure and TTI transmission in the Zhejiang population, which poses a threat to blood safety. It is hoped that expansion of pathogen categories (CMV, EBV, HEV and HTLV-1/2) and blood screening programs will contribute to the future adoption of scientific blood transfusion methods.

Large-Scale Whole-Genome Analysis of HTLV-1-Associated Myelopathy Identified Hereditary Spastic Paraplegias.

Distinguishing human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy from hereditary spastic paraplegia in patients infected with HTLV-1 is challenging due to overlapping clinical symptoms. The aim of this study was to explore the possibility that hereditary spastic paraplegia is inherently present in patients diagnosed with HTLV-1-associated myelopathy. We performed whole-genome sequencing on 315 unrelated patients registered in the HTLV-1-Associated Myelopathy patient registry "HAM-net," from 2013 to 2022 in Japan. CSF inflammatory biomarkers, including CXCL10, were measured. We identified 5 patients with pathogenic variants in the genes RTN2, SPAST, VCP, and UBAP1, which are the known causes of hereditary spastic paraplegia. These patients had no family history of hereditary spastic paraplegia. The levels of CSF inflammatory biomarkers were lower than expected in these patients, compared with disease severity. Genetic analysis is useful for the differentiation of hereditary spastic paraplegia patients from HTLV-1-associated myelopathy patients, especially for the patients with low levels of CSF inflammatory markers. Here we report the presence of hereditary spinal cord diseases in patients diagnosed with HTLV-1-associated myelopathy and provides evidence that genetic analysis would be helpful in the diagnostic workflow.

Seroprevalence of Human T-cell Lymphotropic Virus Types I/II Among Blood Donors in a Tertiary Hospital in Oman.

Routine blood donor screening of human T-cell lymphotropic virus (HTLV) has been practiced in Oman since 2017. Limited data exists on HTLV seroprevalence among Omanis. This study aims to determine the seroprevalence of HTLV-I/II among blood donors attending a hospital-based blood bank to assess the need for a universal versus targeted screening. We conducted a retrospective review of blood donors' results attending a hospital blood bank between January 2017 and February 2020. Blood samples were screened for HTLV-I/II antibodies using ARCHITECT i2000SR. Reactive samples underwent further testing by immunoblot assay (MP Diagnostics HTLV Blot 2.4). Age, gender, and nationality were assessed. All components manufactured at the blood bank undergo leukoreduction before storage. A total of 24 469 first-time blood donors were screened for HTLV antibodies. Most participants were male (n = 22 186, 90.7%), and the majority were Omani (n = 22 711, 92.8%). The age range was 18 to 64 years, with a median of 32 years. The seroreactivity rate was 0.2% (43; 95% CI: 0.12-0.23). Confirmatory testing by immunoblot revealed three indeterminate results (7.9%), of which two were Omani and one non-Omani donor, and the remaining 40 seroreactive donors tested negative. Our study revealed zero seroprevalence of confirmed HTLV among blood donors. The continuation of universal screening for first-time donors is a standard of care. With universal leukoreduction at Sultan Qaboos University Hospital and a very low risk of HTLV in Oman's population, the need for screening regular donors can be reconsidered if these findings are confirmed on a larger scale involving other blood banks in Oman.

Determination of molecular epidemiologic pattern of human T-lymphotropic virus type 1 (HTLV-1) in Alborz province, Iran.

Human T-cell lymphotropic virus type 1 (HTLV-1) is linked to two debilitating diseases, adult T-cell leukemia/lymphoma (ATLL) and HTLV-1 associated myelopathy tropical spastic paraparesis (HAM/TSP), which are prevalent in various parts of the world, including the Alborz province in Iran. Understanding the prevalence and evolutionary relationships of HTLV-1 infections in these endemic areas is of utmost importance. In the realm of phylogenetic studies, long terminal repeat (LTR) region of HTLV-1 stands out as highly conserved, yet more variable compared to other gene segments. Consequently, it is the primary focus for phylogenetic analyses. Additionally, trans-activator of transcription (Tax), an oncoprotein, holds a pivotal role in the regulation of gene expression. This cross-sectional study delved into the phylogenetic analysis of HTLV-1 among individuals in Alborz province of Iran. To confirm infection, we amplified partial sequence LTR (PLTR) and HTLV-1 bZIP factor (PHBZ). For phylogenetic analysis, we sequenced the full sequence LTR (FLTR) andfull Tax sequence (FTax). The FLTR and FTax sequences underwent analysis using BioEdit, and phylogenetic trees were constructed using MEGA-X software. Out of the roughly 15,000 annual blood donors in Alborz, 19 samples tested positive for HTLV-1, indicating a 0.13% HTLV-1 positivity rate among blood donors. Furthermore, the HTLV-1 virus prevalent in the Alborz province belongs to subtype A (cosmopolitan) subgroup A. The findings revealed that while mutations were observed in both the LTR and Tax genes, they were not significant enough to bring about fundamental alterations. Despite positive selection detected in three Alborz isolates, it has not led to mutations affecting Tax function and virulence.

How do socioeconomic determinants of health affect the likelihood of living with HTLV-1 globally? A systematic review with meta-analysis.

Human T Lymphotropic Virus type 1 (HTLV-1) is a neglected retrovirus associated with many clinical disorders, most notably Adult T-cell Leukemia/Lymphoma and HTLV-1-Associated Myelopathy (HAM). Found in endemic clusters across the world, high prevalence has been reported in minoritized groups who suffer from health inequities. This study investigates the association between HTLV-1 prevalence and the following socioeconomic determinants of health: education, income, and employment, which are markers of health inequity. A systematic review was conducted by searching the following databases: Ovid/Medline, Embase, Global Health Database, Web of Science, LILACS and SciELO. Primary studies in English, Spanish and Portuguese mentioning HTLV-1 and one of education, income and/or employment were included. A random-effects meta-analysis was performed, and odds ratios (OR) were calculated to determine the association between these socioeconomic determinants of health and HTLV-1 prevalence. 42 studies were included. The likelihood of having HTLV-1 was higher in individuals with less than completed primary education compared to those who completed primary education (OR 1.86 [95% CI 1.34-2.57]; p < 0.01). This may be because individuals with low education have reduced access to and understanding of health information, thus increasing the prevalence of risk factors associated with HTLV-1 infection. No other determinants were found to be statistically significant. Fewer years of schooling are associated with increased likelihood of contracting HTLV-1. Therefore, health promotion materials and public health policies regarding HTLV-1 must consider those with lower educational levels to effectively reduce disease transmission. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335004, identifier (CRD42022335004).

Disfunción eréctil e infecciones virales: una revisión narrativa

Description of the topic: Erectile dysfunction is a prevalent condition among the male population and can result from various factors such as hormonal, metabolic, infectious, or anatomical issues. Infections caused by viruses such as Human Immunodeficiency Virus (HIV), Herpes Simplex Virus, Varicella-Zoster Virus, Human Papillomavirus (HPV), Human T-lymphotropic Virus type 1 (HTLV-1), Dengue virus, and SARS-CoV-2 have been found to be associated with erectile dysfunction through different physiological mechanisms. In many cases, these infections interact with the immune system, leading to the development of a localized or generalized inflammatory response of varying intensity. Relevance: Certain viral infections can directly affect the tissues of the male reproductive system, resulting in erectile dysfunction. These infections can damage the nerves and blood vessels that are essential for achieving and maintaining an erection. Conclusion: Erectile dysfunction is of multifactorial origin, and according to the reviewed literature it can be triggered by some vascular sequelae induced by viral infections, including those produced by the acquired immunodeficiency virus (HIV), herpes simplex virus, zoster, human papilloma (HPV), human lymphotropic virus type I (HTL1), Dengue and SARS-CoV2.

Heterogeneous nuclear ribonucleoprotein K promotes cap-independent translation initiation of retroviral mRNAs.

Translation initiation of the human immunodeficiency virus-type 1 (HIV-1) genomic mRNA (vRNA) is cap-dependent or mediated by an internal ribosome entry site (IRES). The HIV-1 IRES requires IRES-transacting factors (ITAFs) for function. In this study, we evaluated the role of the heterogeneous nuclear ribonucleoprotein K (hnRNPK) as a potential ITAF for the HIV-1 IRES. In HIV-1-expressing cells, the depletion of hnRNPK reduced HIV-1 vRNA translation. Furthermore, both the depletion and overexpression of hnRNPK modulated HIV-1 IRES activity. Phosphorylations and protein arginine methyltransferase 1 (PRMT1)-induced asymmetrical dimethylation (aDMA) of hnRNPK strongly impacted the protein's ability to promote the activity of the HIV-1 IRES. We also show that hnRNPK acts as an ITAF for the human T cell lymphotropic virus-type 1 (HTLV-1) IRES, present in the 5'UTR of the viral sense mRNA, but not for the IRES present in the antisense spliced transcript encoding the HTLV-1 basic leucine zipper protein (sHBZ). This study provides evidence for a novel role of the host hnRNPK as an ITAF that stimulates IRES-mediated translation initiation for the retroviruses HIV-1 and HTLV-1.

African Environmental Pressures and Carcinogenesis: The Impact on The Lymphomas, the Leukemias, and Breast cancer

The African environment has for millennia been dominated by rampant agents of infections, of which malaria is among the best known, virtually uncontrolled, and associated with lifelong human struggles, ameliorarated by measures as socioeconomicaly affordable. This has led to the emergence of a variety of genetic aberrations, some of which are deleterious, resulting in major disease dysparities, including benign ones like sickle cell disease, and malignancies like the leukaemias, lymphomas, and breast cancer. They include the reduced incidence and the absence of its peak in acute lymphoblastic leukaemia in the first quinquennium of Nigerian children, which is otherwise typically seen in the children of high-income countries. Conversely is the observation in acute myelogenous leukaemia, with its chloroma-associated variant and its incidence peaking in the second quinquennium. This epidemiology is akin to the recent observation of acute myelogenous leukemia among sickle cell disease patients among the people of African descent in California, USA. Chloroma-associated acute myelogenous leukemia, and Burkitt lymphoma are linked with low socioeconomic status, an epidemiological feature that is shared with triple negative breast cancer patients in West Africa and the women of African descent in the United States. While a role for the malaria-associated genetic aberration underlying the Duffy null genotype is confirmed in the diversity of the triple negative breast cancer in the women of West Africa and those of African descent in the United States, it is conceivable, but not yet established in acute myelogenous leukemia. The zoonosis-linked human T-cell lymphotropic virus type 1 infection is associated with at least 17% of non-BL-non-Hodgkin lymphoma in form of its sentinel disease, the adult T-lymphoma/leukemia, but unexpicably much lower than the 50-60% of other major endemic zones of Japan and the African descendants of the Caribeean. This report describes the clinical, laboratory, and epidemiological features of leukemia and lymphoma cases diagnosed between 1982 and 1984 in the city of Ibadan, Nigeria, some of the features of which are reminiscent of the observations of Ludwig Gross’s experiments on environmental influences, such as malnutrition and infections, on animal leukemogenesis. These events are the consequences of the primordial pressures that have shaped human genetics and pathophysiology. Evidence provided in this study, indicating association of increasing socioeconomic status with increasing frequency of the c-ALL subtype, is indicative of the prospects for leukemogenesis of acute lymphoblastic leukemia and its epidemiology in Nigerians. Some findings reported here indicate the influence of the African genetic ancestry in the etiology of acute myelogenous leukemia, while socioecomic status is linked to the etiology of childhood acute lymphoblastic leukemia, as well as a variant of chronic lymphocytic leukemia, and the chloroma-associated acute myelogenous leukemia. These observations are suggestive of the existence of pathways to etiological discoveries in the leukemias. Observations reviewed in this paper reflect examples of changes that have occurred over the past 200 years in the societal perception of health challenges among the new-found communities of colonial Africa and the Americas - from the reductionistic connotations such as in the “virgin-soil theory” - towards that of social determinants of health.

T-Acute Lymphoblastic Leukemia

Abstract Acute lymphoblastic leukemia (ALL) is a condition in which immature white blood cells (WBCs) accumulate in the bone marrow, resulting in the crowding of normal WBCs and buildup in the liver, spleen, and lymph nodes. ALL is a malignancy of B or T lymphoblasts. B lymphocytes protect the body against bacteria and viruses through production of antibodies, which can directly destroy target cells or trigger others to do so. T lymphocytes directly destroy bacteria or cells infected with viruses. Approximately 20% of all ALL patients are categorized specifically to suffer from T-cell ALL (T-ALL), and it is seen to be more prevalent in the adult population in comparison with children, with incidences shown to diminish with age. Among T-ALL cases in the pediatric population, a median onset of age 9 has been identified and the disease is particularly prominent among adolescents. The disease stems from cytogenic and molecular abnormalities, resulting in disruption of developmental pathways controlling thymocyte development, tumor suppressor development, and alterations in control of cell growth and proliferation. Distinct from adult T-cell leukemia where T-cell lymphotropic virus type I causes malignant maturation of T cells, T-ALL is a precursor for lymphoid neoplasm. Its clinical presentation most commonly includes infiltration of the central nervous system and further identifies mediastinal mass presence originating from the thymus, along with extramedullary involvement of multiple organs including the lymph node as a result of hyperleukocytosis.

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.

Human T-cell lymphotropic virus type 1-related uveitis, review about a case

Abstract Human T-cell lymphotropic virus type 1 (HTLV-1) is an endemic retrovirus associated with adult T-cell leukemia/lymphoma (ATL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM-TSP), and HTLV-1 uveitis (HU). The latter may occur in association with HAM-TSP, more rarely along ATL, or as an isolated manifestation of the viral infection. The authors present a review of the literature on HU, illustrated by a clinical case. A literature search was performed in the MEDLINE database (PubMed) and included surveys completed until 2022. HU prevalence is increasing in nonendemic metropolitan areas due to migration, thus it is becoming an increasingly relevant agent in the differential diagnosis of patients with uveitis.

Microbes and Mental Illness: Past, Present, and Future.

A review of the association between microbes and mental illness is performed, including the history, relevant definitions, infectious agents associated with mental illnesses, complex interactive infections, total load theory, pathophysiology, psychoimmunology, psychoneuroimmunology, clinical presentations, early-life infections, clinical assessment, and treatment. Perspectives on the etiology of mental illness have evolved from demonic possession toward multisystem biologically based models that include gene expression, environmental triggers, immune mediators, and infectious diseases. Microbes are associated with a number of mental disorders, including autism, schizophrenia, bipolar disorder, depressive disorders, and anxiety disorders, as well as suicidality and aggressive or violent behaviors. Specific microbes that have been associated or potentially associated with at least one of these conditions include Aspergillus, Babesia, Bartonella, Borna disease virus, Borrelia burgdorferi (Lyme disease), Candida, Chlamydia, coronaviruses (e.g., SARS-CoV-2), Cryptococcus neoformans, cytomegalovirus, enteroviruses, Epstein-Barr virus, hepatitis C, herpes simplex virus, human endogenous retroviruses, human immunodeficiency virus, human herpesvirus-6 (HHV-6), human T-cell lymphotropic virus type 1, influenza viruses, measles virus, Mycoplasma, Plasmodium, rubella virus, Group A Streptococcus (PANDAS), Taenia solium, Toxoplasma gondii, Treponema pallidum (syphilis), Trypanosoma, and West Nile virus. Recognition of the microbe and mental illness association with the development of greater interdisciplinary research, education, and treatment options may prevent and reduce mental illness morbidity, disability, and mortality.

DETECTION OF EPSTEIN-BARR VIRUS GENOME IN PEDIATRIC PATIENTS WITH LEUKEMIA AND HODGKIN LYMPHOMA: VIRAL ETIOLOGY IN PEDIATRIC CANCERS IN TÜRKİYE

Objective: Cancer is a pervasive disease characterized by its widespread occurrence and challenging treatment process. While numerous agents, including viruses, have been identified as potential causes of cancer in both adults and children, the complete pathogenesis of cancers remains incompletely elucidated. This study aimed to examine the presence of four viral agents, namely Human T-cell Lymphotropic Virus Type 1 (HTLV-1), Epstein-Barr Virus (EBV), Kaposi's Sarcoma- Associated Herpesvirus (KSHV), and Human Parvovirus B19 (HPV B19), in blood samples obtained from pediatric patients (n=64) diagnosed with B cell acute lymphoblastic leukemia (ALL), T cell ALL, Hodgkin lymphoma, and patients with relapsed leukemia and lymphoma. &#x0D; Material and Methods: The whole blood samples collected from the patients during the pre-treatment and post-treatment periods underwent polymerase chain reaction (PCR) and real- time PCR to identify the presence of the viral genomes of HTLV-1, EBV, KSHV, and HPV B19. The samples that tested positive were subsequently subjected to Sanger sequencing, followed by phylogenetic analysis. &#x0D; Results: Among a total of 64 samples analyzed, HTLV-1, KSHV, and HPV B19 were found to be negative. However, EBV genome was detected in six samples (9.37%) from patients with ALL and Hodgkin lymphoma, comprising both pre- treatment (n=3) and post-treatment (n=3) cases. Subsequent sequencing and alignment of the positive EBV samples with other EBV sequences deposited in GenBank revealed a high degree of similarity. &#x0D; Conclusion: Our findings suggest that EBV may be one of the viral agents implicated in pediatric cancer cases involving leukemia and Hodgkin lymphoma. Therefore, it is recommended to consider testing for the presence of EBV genome in these patient populations within the context of Türkiye. This information contributes to a better understanding of the viral etiology underlying pediatric cancers, enabling the development of targeted diagnostic and therapeutic strategies in the future.

Nonpharmacological interventions and outcomes in the management of complications of human T-cell lymphotropic virus type 1-related myelopathy/tropical spastic paraparesis: A systematic review.

Human T-cell lymph tropic virus type 1 (HTLV-I)-related myelopathy/tropical spastic paraparesis (TSP) is a progressive inflammatory process affecting the spinal cord that occurs as a result of HTLV 1. The use of nonpharmacological approaches has always been one of the treatment strategies in these patients, but disagreement about these interventions and their results has led to their limited use. Therefore, this study aimed to identify nonpharmacological interventions and their consequences in these patients. We followed the Cochrane Handbook for systematic reviews of interventions. The present report is organized according to the preferred reporting items for systematic reviews and meta-analyses. This study was conducted at PubMed, Cochrane Library, Web of Science, and Scopus, among all published studies by December 30, 2021. Keywords were: HTLV-1, Human T-lymph tropic virus 1, HTLV-I-associated myelopathy, HAM/TSP, tropical spastic paraparesis, nonpharmacological intervention, nonpharmacological treatment, massage, physiotherapy, acupuncture, acupressure, and exercise. The quality of the studies was assessed using JADAD. Of 288 articles, 11 were eligible for data extraction published between 2014 and 2021. 90/9% of studies were randomized clinical trials. 81/8% of articles were of high quality. The total sample size was 253 people, of which 137 (54/15%) were women. Approaches such as exercise and motion therapy, electrotherapy, behavioral therapy, and virtual reality can be used for these patients. With these interventions, results such as improved mobility and balance, physical condition, pain, quality of life, muscle spasticity, maximum inspiratory pressure, and urinary symptoms can be achieved. The most common physical therapy method used in studies was active and passive body movements, which are associated with positive results for patients. Due to the small sample size in this group of studies, it is necessary to conduct more clinical trials for more accurate conclusions. Furthermore, due to the limited number of studies that have used electrical stimulation or combined intervention packages, it is not possible to say with certainty what effect these methods have on patients. It is necessary to conduct more clinical trials.

AICAR Induces AMPK-Independent Cell Death in Adult T-Cell Leukemia/Lymphoma and Has Anti-Tumor Activity

Introduction: Adult T-cell leukemia/lymphoma (ATL) is an aggressive T cell leukemia/lymphoma caused by human T-cell lymphotropic virus type I (HTLV-1) and has a poor outcome. Recently, we reported that AMPKα, the catalytic unit of AMP-activated protein kinase (AMPK), is highly expressed in cells from patients with ATL and that an AMPK inhibitor had anti-tumor activity in ATL mice 1. On the other hand, acadesine or 5-aminoimidazole-4-carboxamide riboside (AICAR) is anAMPK activator, and was recently shown to have tumor suppressive effects on B cell chronic lymphocytic leukemia via the activation of AMPK. However, the effect of AICAR on the death of ATL-related cell lines is unknown. This study evaluated the effects of AICAR on death in ATL-related cell lines and its anti-tumor activity. Results: We demonstrated that AICAR inhibited the proliferation of ATL-related cell lines (S1T, MT-1 and MT-2) but not non-HTLV-1-infected Jurkat cells and peripheral blood mononuclear cells from healthy individuals. However, AICAR did not increase the phosphorylation levels of AMPKα. We found that AICAR increased annexin V-positive cell numbers in the sub-G0/G1 phase, and decreased the mitochondrial membrane potential and caspase-3/8/9 activation, which are hallmarks of apoptosis. However, AICAR did not increase the phosphorylation levels of AMPKα. On the other hand, HTLV-1 Tax, an HTLV-1-encoded oncogenic factor, expression did not affect AICAR-induced cell death. Moreover, AICAR induced the expression of death receptors (DR) DR4 and DR5 in vitro. Furthermore, AICAR inhibited the growth and infiltration of S1T cells transplanted subcutaneously in NOD/SCID/gamma mice. Conclusion: This is the first evidence to demonstrate the AMPK-independent effects of AICAR on death in ATL-related cell lines and its anti-tumor activity. Thus, AICAR might be a candidate for the treatment of ATL. Disclosures : No relevant conflicts of interest to declare. 1. Aikawa A, Kozako T, Uchida Y, et al. Cell death induced by dorsomorphin in adult T-cell leukemia/lymphoma is AMPK-independent. Febs j. 2020;287(18):4005-4015.

Anti-tumor activity of 5-aminoimidazole-4-carboxamide riboside with AMPK-independent cell death in human adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T cell leukemia/lymphoma caused by human T-cell lymphotropic virus type I (HTLV-1). Acadesine or 5-aminoimidazole-4-carboxamide riboside (AICAR) is an AMP-activated protein kinase (AMPK) activator that was recently shown to have tumor suppressive effects on B cell chronic lymphocytic leukemia, but not ATL. This study evaluated the cytotoxic effects of AICAR on ATL-related cell lines and its anti-tumor activity. Here, we demonstrated that AICAR induced cell death via apoptosis and the mitochondrial membrane depolarization of ATL-related cell lines (S1T, MT-1, and MT-2) but not non-HTLV-1-infected Jurkat cells. However, AICAR did not increase the phosphorylation levels of AMPKα. In addition, AICAR increased the expression of the death receptors (DR) DR4 and DR5, and necroptosis-related proteins including phosphorylated receptor-interacting protein family members and the mixed lineage kinase domain-like protein. Interestingly, HTLV-1 Tax, an HTLV-1-encoded oncogenic factor, did not affect AICAR-induced apoptosis. Furthermore, AICAR inhibited the growth of human ATL tumor xenografts in NOD/SCID/gamma mice in vivo. Together, these results suggest that AICAR induces AMPK-independent cell death in ATL-related cell lines and has anti-tumor activity, indicating that it might be a therapeutic agent for ATL.

Immune response to COVID-19 vaccines among people living with human T-cell lymphotropic virus type 1 infection: a retrospective cohort study from Iran.

The effectiveness of COVID-19 vaccination is still unclear in individuals with underlying diseases such as HTLV-1 infection. This retrospective cohort study aimed to evaluate the humoral response of COVID-19 vaccines among people living with HTLV-1 (PLHTLV) in northeastern Iran. From December 2021 to October 2022, eighty-six HTLV-1+ subjects (50 males and 36 females; 47.7 ± 11.2 years) and 90 HTLV-1 seronegative individuals (age- and sex-matched convenient samples) were enrolled. The humoral immune response was evaluated by measuring different COVID-19 Abs in serum samples at least 28 days after receiving 2nd or 3rd doses of COVID-19 vaccines. Throughout all three rounds of immunization, Sinopharm was the most commonly used COVID-19 vaccine across all three immunization rounds. Compared to the HTLV-1- group, a significantly lower frequency of all four Abs activity was observed among PLHTLV:anti-nucleocapsid (66.3% vs 86.7%, p = 0·001), anti-spike (91.9% vs 98.9%, p = 0·027), RBD (90.7% vs 97.8%, p = 0·043), and neutralizing Abs (75.6% vs 95.5%, p < 0·001). Also, the frequency of all Abs in 28 patients with HAM/TSP was higher than that of 58 asymptomatic carriers, although this difference was statistically significant only in the case of anti-spike Abs (p = 0.002). Notably, PLHTLV-vaccinated against COVID-19 demonstrated significantly lower antibody activities, indicating a reduced humoral immune response to COVID-19 vaccines.

Human tumor viruses: induction of three-dimensional alterations in the host genome structure.

Certain viruses called tumor viruses or oncoviruses are capable to change the gene expression pattern of distinct human or animal cell types in tissue culture, resulting in uncontrolled proliferation as well as a change in the social behavior of the infected cells: the oncovirus-transformed, immortalized cells are capable to form malignant neoplasms in suitable animal models. At present, seven human viruses are categorized as causative agents of distinct human malignancies. The genomes of human tumor viruses, typically encode viral oncoproteins and non- translated viral RNAs that affect the gene expression pattern of their target cells or induce genetic and epigenetic alterations contributing to oncogenesis. Recently, the application of chromatin conformation capture technologies and three-dimensional (3D) molecular imaging techniques revealed how the gene products or genomes of certain human tumor viruses interact with and induce alterations in the 3D host genome structure. This Mini Review aims to cover selected aspects of these developments. The papers, discussed briefly, describe how insertion of a novel viral binding site for the 3D genome organizer cellular protein CCCTC-binding factor (CTCF) into the DNA of T cells infected by human T-cell lymphotropic virus type 1 (HTLV-1) may contribute to lymphomagenesis, as well as how integration of high risk human papillomavirus genome into the host cell DNA may facilitate cervical carcinogenesis. Recent results regarding the interactions of cellular genomes with the episomal, chromatinized DNA genomes of oncogenic human herpesvirus, Epstein-Barr virus (EBV) will also be summarized, similarly to available data regarding contacts formed by episomal or integrated hepatitis B virus (HBV) DNA with host chromatin. Finally, a putative mechanism of hepatitis C virus (HCV) induced chromatin alterations will be presented, which may solve the riddle, how a cytoplasmic RNA virus without a viral oncogene could induce malingnant transfrormation of hepatocytes.

Cancers Attributable to Infections in the US in 2017

Infections are largely modifiable causes of cancer. However, there remains untapped potential for preventing and treating carcinogenic infections in the US. To estimate the percentage and number of incident cancers attributable to infections in the US among adults and children for the most recent year cancer incidence data were available (2017). A literature search from 1946 onward was performed in MEDLINE on January 6, 2023, to obtain the data required to calculate population attributable fractions for 31 infection-cancer pairs. National Health and Nutrition Examination Survey data were used to estimate the population prevalence of hepatitis B and C viruses and Helicobacter pylori. Studies conducted in the US or other Western countries were selected according to specific infection-cancer criteria. Data from 128 studies were meta-analyzed to obtain the magnitude of an infection-cancer association or prevalence of the infection within cancer cells. The proportion of cancer incidence attributable to 8 infections. Of the 1 666 102 cancers diagnosed in 2017 among individuals aged 20 years or older in the US, 71 485 (4.3%; 95% CI, 3.1%-5.3%) were attributable to infections. Human papillomavirus (n = 38 230) was responsible for the most cancers, followed by H pylori (n = 10 624), hepatitis C virus (n = 9006), Epstein-Barr virus (n = 7581), hepatitis B virus (n = 2310), Merkel cell polyomavirus (n = 2000), Kaposi sarcoma-associated herpesvirus (n = 1075), and human T-cell lymphotropic virus type 1 (n = 659). Cancers with the most infection-attributable cases were cervical (human papillomavirus; n = 12 829), gastric (H pylori and Epstein-Barr virus; n = 12 565), oropharynx (human papillomavirus; n = 12 430), and hepatocellular carcinoma (hepatitis B and C viruses; n = 10 017). The burden of infection-attributable cancers as a proportion of total cancer incidence ranged from 9.6% (95% CI, 9.2%-10.0%) for women aged 20 to 34 years to 3.2% (95% CI, 2.4%-3.8%) for women aged 65 years or older and from 6.1% (95% CI, 5.2%-7.0%) for men aged 20 to 34 years to 3.3% (95% CI, 1.9%-4.4%) for men aged 65 years or older. Among those aged 19 years or younger, 2.2% (95% CI, 1.3%-3.0%) of cancers diagnosed in 2017 were attributable to Epstein-Barr virus. Infections were estimated to be responsible for 4.3% of cancers diagnosed among adults in the US in 2017 and, therefore, represent an important target for cancer prevention efforts.

Poor Outcome of Adult T-Cell Leukemia/Lymphoma with Current Available Therapy: An Experience of Two Centers

Introduction: Adult T-cell leukemia lymphoma (ATLL) is an aggressive mature T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1) infection. Despite its poor prognosis, there is no standard therapy for ATLL due to its low incidence and the disease affecting only endemic geographical clusters. Methods: A retrospective evaluation of patients with the diagnosis of ATLL at Moffitt Cancer Center and Memorial Healthcare System was done to identify patients and disease characteristics along with the progression-free survival (PFS) and overall survival (OS) for the different therapies used. Results: The 61 patients analyzed showed a median age of 58 with 82.5% of them being of African American descent. The acute variant contributed to the majority of cases (43.9%), followed by 36.8% presenting as a lymphoma variant. There was no statistical difference in the PFS (6.4 m, 3.1 m, 2.1 m; p = 0.23) or OS (14 m, 8.9 m, 18.5 m; p = 0.14) between cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), intensive chemotherapy regimens, and other modalities, respectively. However, the patients who had complete or partial remission with first-line therapy had better OS (15.9 m vs. 7.2 m; p = 0.004). Conclusions: The study highlighted the poor outcome of the current regimens and the lack of a unifying protocol for this vicious disease. The acute variants were treated with more intensive regimens, but there was no difference in the OS between the three major options of CHOP, intensified chemotherapy, and others. This underscores the need for more clinical trials to develop better outcomes.