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Expert Review of Anti-infective Therapy May 2024Human T-cell leukemia virus type 1 (HTLV-1) carriers may develop adult T-cell leukemia (ATL), or HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP)....
INTRODUCTION
Human T-cell leukemia virus type 1 (HTLV-1) carriers may develop adult T-cell leukemia (ATL), or HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The evidence is limited regarding other diseases potentially associated with HTLV-1, such as HTLV-1-associated autoimmune diseases.
AREA COVERED
We summarized the available information on complications associated with HTLV-1 infection.
EXPERT OPINION
Previous studies showed that HTLV-1 carriers have an increased incidence of collagen diseases including Sjögren's syndrome, as well as dysthyroidism, diabetes mellitus, and atherosclerosis. Furthermore, cognitive deficits are observed in asymptomatic carriers and in symptomatic carriers who develop HAM/TSP. It is hypothesized that altered immunoregulation occurs as a result of persistent HTLV-1 infection. A systematic review and meta-analysis demonstrated that HTLV-1 infection itself has an adverse impact on overall survival. ATL alone cannot entirely explain the adverse impact of HTLV-1 infection on overall mortality, because the incidence is low, and therefore HTLV-1-associated diseases as a whole may contribute to the inferior clinical outcome. However, there are insufficient data to determine the causal relationship between HTLV-1 infection and each complication. While non-cancerous events linked to HTLV-1 infection are not fatal, they are likely to reduce quality of life. Large prospective studies should be conducted by international collaborators.
Topics: Humans; Autoimmune Diseases; Carrier State; HTLV-I Infections; Human T-lymphotropic virus 1; Leukemia-Lymphoma, Adult T-Cell; Paraparesis, Tropical Spastic
PubMed: 38536666
DOI: 10.1080/14787210.2024.2336547 -
The American Journal of Tropical... May 2024Co-occurrence of paracoccidioidomycosis and strongyloidiasis in immunosuppressed patients, particularly those infected with human T-lymphotropic virus type 1/2, is...
Co-occurrence of paracoccidioidomycosis and strongyloidiasis in immunosuppressed patients, particularly those infected with human T-lymphotropic virus type 1/2, is infrequent. We describe the case of a Peruvian farmer from the central jungle with human T-lymphotropic virus type 1/2 infection, with 2 months of illness characterized by respiratory and gastrointestinal symptoms associated with fever, weight loss, and enlarged lymph nodes. Strongyloides stercoralis and Paracoccidioides brasiliensis were isolated in sputum and bronchoalveolar lavage samples, respectively. The clinical evolution was favorable after the patient received ivermectin and amphotericin B. We hypothesize that autoinfestation by S. stercoralis in human T-lymphotropic virus type 1/2-infected patients may contribute to the disseminated presentation of Paracoccidioides spp. Understanding epidemiological context is crucial for suspecting opportunistic regional infections, particularly those that may coexist in immunosuppressed patients.
Topics: Humans; Paracoccidioidomycosis; Strongyloidiasis; Male; HTLV-I Infections; Animals; Ivermectin; Strongyloides stercoralis; Human T-lymphotropic virus 1; Paracoccidioides; Coinfection; HTLV-II Infections; Immunocompromised Host; Amphotericin B; Antifungal Agents; Adult
PubMed: 38531110
DOI: 10.4269/ajtmh.23-0171 -
AIDS Reviews 2024Sweden is a country with a low prevalence of human lymphotropic T-cell virus (HTLV) infection, estimated at < 0.005%, but the infection rate is notably higher in... (Review)
Review
Sweden is a country with a low prevalence of human lymphotropic T-cell virus (HTLV) infection, estimated at < 0.005%, but the infection rate is notably higher in specific risk groups such as HTLV-2 among intravenous drug users (IVDU) and people originating from HTLV-1 highly endemic areas. Thus, in the most recent study from 2012, the prevalence of HTLV-2 among IVDU in Stockholm was 3.2%. However, much of the epidemiological data on HTLV in Sweden stems from studies conducted primarily between the 1990s and 2007, and the impact of migration to Sweden during the past 15 years has not been evaluated. Despite Sweden's status as a country with generally low prevalence of HTLV, it is prudent to anticipate and prepare for several potential challenges associated with HTLV infection in the future. Proactive measures to enhance awareness, alongside strategies to curtail transmission and mitigate complications, are crucial for addressing this relatively rare, but significant health issue. In this work, we review the current epidemiological knowledge about HTLV in Sweden and discuss future Swedish perspectives.
Topics: Humans; Human T-lymphotropic virus 1; Sweden; HIV Infections; Substance Abuse, Intravenous; T-Lymphocytes; HTLV-I Infections
PubMed: 38530748
DOI: 10.24875/AIDSRev.24000002 -
Journal of Veterinary Research Mar 2024Bovine leukaemia virus (BLV) is a Deltaretrovirus responsible for enzootic bovine leukosis, the most common neoplastic disease of cattle. It deregulates the immune...
INTRODUCTION
Bovine leukaemia virus (BLV) is a Deltaretrovirus responsible for enzootic bovine leukosis, the most common neoplastic disease of cattle. It deregulates the immune system, favouring secondary infections and changes in the blood and lymphatic tissues. Blood homeostasis depends on functional haematopoietic stem cells (HSCs). Bone marrow is populated by these cells, which express CD34 and CD35 surface antigens and produce and release cytokines involved in the maintenance of haematopoiesis. The aim of the study was determination of the profile of cytokine production by CD34 stem cells of cattle naturally infected with BLV.
MATERIAL AND METHODS
The HSCs were generated from the blood and lymphoid organs of cows infected with BLV and healthy control cows with immunomagnetic separation and anti-CD34 monoclonal antibodies. Isolated CD34 cells were cultivated for two weeks with interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor. The levels of IL-6, IL-10, IL-12p40, IL-12p70, interferon gamma (IFN-γ) and tumour necrosis factor alpha (TNF-α) were determined in culture fluid by flow cytometry.
RESULTS
The expression of IL-6, IL-12p70 and TNF-α in blood HSCs was higher in BLV cows than in the control animals. In bone marrow HSCs of infected cows, IL-12, TNF-α and IFN-γ were more concentrated, but in these cows' spleen HSCs only expression of IL-10 was elevated. In HSCs isolated from the lymph nodes of leukaemic cows, only TNF-α secretion was lower than in control cows, the other cytokines being more potently secreted.
CONCLUSION
Infection with BLV caused statistically significant differences in cytokine expression by HSC CD34 cells.
PubMed: 38525233
DOI: 10.2478/jvetres-2024-0012 -
International Journal of Infectious... Jun 2024Human T-lymphotropic viruses (HTLV)-1 infection is endemic in many countries of Central and South America and Caribbean (CSA&C). Neither screening nor surveillance... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human T-lymphotropic viruses (HTLV)-1 infection is endemic in many countries of Central and South America and Caribbean (CSA&C). Neither screening nor surveillance programs exist for HTLV-1/2 infection among pregnant women in this region. Neither in Western nations with large migrant flows from HTLV-1/2 endemic regions.
METHODS
Systematic review and meta-analysis of the prevalence of HTLV-1/2 infection among CSA&C pregnant women. We included studies searching EMBASE, PubMed/MEDLINE, Scopus, and Web of Science from inception to February 15, 2023. This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines.
RESULTS
We identified a total of 620 studies. Only 41 were finally included in the meta-analysis. Most studies (61.0%) were from Brazil and Peru (14.6%). The total number of participants was 343,707. The pooled prevalence of HTLV-1/2 infection among CSA&C pregnant women was 1.30% (95% CI: 0.96-1.69) using anti-HTLV-1/2 antibody screening tests. There was a high heterogeneity (I = 98.6%). Confirmatory tests gave an HTLV-1 infection rate of 1.02% (95% CI: 0.75-1.33).
CONCLUSIONS
The prevalence of HTLV-1/2 infection among CSA&C pregnant women is 1.3%, most cases being HTLV-1. This rate is greater than for other microbial agents regularly checked as part of antenatal screening (such as HIV, hepatitis B, or syphilis). Thus, HTLV-1/2 antenatal testing should be mandatory among CSA&C pregnant women everywhere.
Topics: Humans; Pregnancy; Female; HTLV-I Infections; HTLV-II Infections; Prevalence; Caribbean Region; South America; Human T-lymphotropic virus 1; Pregnancy Complications, Infectious; Human T-lymphotropic virus 2; Central America
PubMed: 38522611
DOI: 10.1016/j.ijid.2024.107018 -
Journal of the Neurological Sciences Apr 2024HTLV-1 is a retrovirus virus that infects CD4+ T cells. Most people with HTLV-1 infection remain asymptomatic but some may develop conditions such as HTLV-1 associated... (Review)
Review
HTLV-1 is a retrovirus virus that infects CD4+ T cells. Most people with HTLV-1 infection remain asymptomatic but some may develop conditions such as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T-cell leukemia/lymphoma. HAM/TSP is characterized by progressive spasticity and weakness of the lower extremities, as well as loss of bladder control and sensory disturbances. The risk of developing HAM/TSP is associated with the duration of infection and the proviral load. There is currently no cure for the disease but medications can help manage symptoms and slow the progression of the disease. This is the case of a 66-year-old female who presented with nonspecific symptoms of weakness and spasticity in a hospital in Connecticut and was subsequently diagnosed with HAM/TSP. The patient's diagnosis highlights the importance of considering diseases previously confined to specific endemic regions in a globalized world where increased emigration and population mixing can occur. Early identification and management of such cases is essential for optimizing patient outcomes and quality of life.
Topics: Adult; Female; Humans; Aged; Paraparesis, Tropical Spastic; Human T-lymphotropic virus 1; Quality of Life; HTLV-I Infections; Risk Factors
PubMed: 38520941
DOI: 10.1016/j.jns.2024.122973 -
Proceedings of the National Academy of... Mar 2024Human retroviruses are derived from simian ones through cross-species transmission. These retroviruses are associated with little pathogenicity in their natural hosts,...
Human retroviruses are derived from simian ones through cross-species transmission. These retroviruses are associated with little pathogenicity in their natural hosts, but in humans, HIV causes AIDS, and human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia-lymphoma (ATL). We analyzed the proviral sequences of HTLV-1, HTLV-2, and simian T-cell leukemia virus type 1 (STLV-1) from Japanese macaques () and found that APOBEC3G (A3G) frequently generates G-to-A mutations in the HTLV-1 provirus, whereas such mutations are rare in the HTLV-2 and STLV-1 proviruses. Therefore, we investigated the mechanism of how HTLV-2 is resistant to human A3G (hA3G). HTLV-1, HTLV-2, and STLV-1 encode the so-called antisense proteins, HTLV-1 bZIP factor (HBZ), Antisense protein of HTLV-2 (APH-2), and STLV-1 bZIP factor (SBZ), respectively. APH-2 efficiently inhibits the deaminase activity of both hA3G and simian A3G (sA3G). HBZ and SBZ strongly suppress sA3G activity but only weakly inhibit hA3G, suggesting that HTLV-1 is incompletely adapted to humans. Unexpectedly, hA3G augments the activation of the transforming growth factor (TGF)-β/Smad pathway by HBZ, and this activation is associated with ATL cell proliferation by up-regulating and . In contrast, the combination of APH-2 and hA3G, or the combination of SBZ and sA3G, does not enhance the TGF-β/Smad pathway. Thus, HTLV-1 is vulnerable to hA3G but utilizes it to promote the proliferation of infected cells via the activation of the TGF-β/Smad pathway. Antisense factors in each virus, differently adapted to control host cellular functions through A3G, seem to dictate the pathogenesis.
Topics: Humans; Cell Line; Virulence; Human T-lymphotropic virus 1; Leukemia-Lymphoma, Adult T-Cell; Proviruses; Transforming Growth Factor beta; Basic-Leucine Zipper Transcription Factors; APOBEC-3G Deaminase
PubMed: 38502701
DOI: 10.1073/pnas.2309925121 -
Chemical & Pharmaceutical Bulletin 2024The inhibition mode of a retro-inverso (RI) inhibitor containing a hydroxyethylamine dipeptide isostere against the human T-cell leukemia virus type-1 (HTLV-1) protease...
The inhibition mode of a retro-inverso (RI) inhibitor containing a hydroxyethylamine dipeptide isostere against the human T-cell leukemia virus type-1 (HTLV-1) protease was examined. Enzymatic evaluation of the RI-modified inhibitor containing a D-allo-Ile residue revealed that HTLV-1 was competitively inhibited. IC values of the RI-modified inhibitor and pepstatin A, a standard inhibitor of aspartic proteases, were nearly equivalent.
Topics: Humans; Amino Acid Sequence; Aspartic Acid Endopeptidases; Human T-lymphotropic virus 1; Dipeptides; Protease Inhibitors
PubMed: 38479891
DOI: 10.1248/cpb.c23-00879 -
Leukemia Research Mar 2024Adult T-cell leukemia/lymphoma (ATL), caused by human T-cell leukemia virus type-1 (HTLV-1) infection, is a malignant hematologic cancer that remains difficult to cure....
Adult T-cell leukemia/lymphoma (ATL), caused by human T-cell leukemia virus type-1 (HTLV-1) infection, is a malignant hematologic cancer that remains difficult to cure. We herein established a biomarker identification strategy based on the total cell proteomics of cultured ATL cells to search for novel ATL biomarkers. Four protocols with a combination of selected conditions based on lysis buffers and addition agents for total cell proteomics were used for a differential analysis between the ATL cell group (consisting of 11 cell lines), HTLV-1-infected cell group (consisting of 6 cell lines), and HTLV-1-negative cell group (consisting of 6 cell lines). In the analysis, we identified 24 and 27 proteins that were significantly increased (ratio ≥2.0, p < 0.05) and decreased (ratio ≤ 0.5, p < 0.05), respectively, in the ATL group. Previously reported CCL3 and CD30/TNFRSF8 were confirmed to be among significantly increased proteins. Furthermore, correlation analysis between identified proteins and Tax suggested that RASSF2 and GORASP2 were candidates of novel Tax-regulated factors. The biomarker identification strategy established herein is expected to contribute to the identification of biomarkers for ATL and other diseases.
Topics: Adult; Humans; Leukemia-Lymphoma, Adult T-Cell; Proteomics; Human T-lymphotropic virus 1; Biomarkers; Digestion; Lymphoma; Gene Products, tax; Golgi Matrix Proteins
PubMed: 38452534
DOI: 10.1016/j.leukres.2024.107454 -
Journal of Neurology Jun 2024Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. This multicenter,... (Randomized Controlled Trial)
Randomized Controlled Trial
Multicenter, randomized, double-blind, placebo-controlled phase 3 study of mogamulizumab with open-label extension study in a minimum number of patients with human T-cell leukemia virus type-1-associated myelopathy.
Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. This multicenter, randomized phase 3 study evaluated the efficacy and safety of 0.3 mg/kg intravenous mogamulizumab, a monoclonal antibody targeting-CC chemokine receptor 4, every 12 weeks in HAM/TSP patients. This study comprised a 24-week double-blind, placebo-controlled period, 24-week open-label period, and extension treatment period. The primary endpoint was the proportion of patients with a ≥ 1-grade improvement in the Osame motor disability score (OMDS). Secondary endpoints were changes in HTLV-1 proviral load, 10-m timed walk, cerebrospinal fluid (CSF) neopterin levels, and safety. The exploratory endpoint was CSF chemokine C-X-C motif ligand 10 (CXCL10) levels. Thirty-four and 33 patients were randomized to mogamulizumab and placebo arms, respectively. At the end of the double-blind period, no significant difference was found in the OMDS improvement rate or other secondary efficacy endpoints assessing motor activities. However, the mogamulizumab arm showed a significant decrease in HTLV-1 proviral load (- 59.39 ± 29.91% vs. placebo 2.32 ± 36.31%) and CSF neopterin (p < 0.001)/CXCL10 levels (p = 0.004). The baseline OMDS pattern and the 60-80% HTLV-1 proviral load reduction were sustained through the open-label and extension treatment periods. Although a higher incidence of rash (69.2%) was reported, the safety profile was similar compared with a previous phase 1/2a study. We found no significant difference in clinical benefit; however, mogamulizumab may provide long-term clinical benefit by preventing disease progression, as CSF neopterin/CXCL10 levels are associated with long-term prognosis in HAM/TSP.Clinical Trial Registration Number: NCT03191526 (registered date: 6-June-2017).
Topics: Humans; Double-Blind Method; Antibodies, Monoclonal, Humanized; Male; Middle Aged; Female; Paraparesis, Tropical Spastic; Adult; Aged; Neopterin; Human T-lymphotropic virus 1; Chemokine CXCL10; Viral Load; Treatment Outcome
PubMed: 38430272
DOI: 10.1007/s00415-024-12239-x