-
Ocular Immunology and Inflammation Sep 2023Human T-cell leukemia virus type 1 (HTLV-1) is a human retrovirus that causes T-cell malignant diseases (adult T-cell leukemia/lymphoma) and HTLV-1-related non-malignant... (Review)
Review
Human T-cell leukemia virus type 1 (HTLV-1) is a human retrovirus that causes T-cell malignant diseases (adult T-cell leukemia/lymphoma) and HTLV-1-related non-malignant inflammatory diseases, such as HTLV-1 uveitis. Although the symptoms and signs of HTLV-1 uveitis are nonspecific, intermediate uveitis with various degrees of vitreous opacity is the most common clinical presentation. It can occur in one or both eyes and its onset is acute or subacute. Intraocular inflammation can be managed with topical and/or systemic corticosteroids; however, recurrence of uveitis is common. The visual prognosis is generally favorable, but a certain proportion of patients have a poor visual prognosis. Systemic complications of patients with HTLV-1 uveitis include Graves' disease and HTLV-1-associated myelopathy/tropical spastic paraparesis. This review describes the clinical characteristics, diagnosis, ocular manifestations, management, and immunopathogenic mechanisms of HTLV-1 uveitis.
Topics: Adult; Humans; Human T-lymphotropic virus 1; HTLV-I Infections; Uveitis; Eye; Graves Disease; Vision Disorders; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell
PubMed: 36803501
DOI: 10.1080/09273948.2023.2175697 -
Current Opinion in Virology Feb 2023Adult T-cell leukemia/lymphoma (ATLL) is an aggressive hematologic malignancy linked to HTLV-1 infection, which is refractory to therapy. The precise mechanism of... (Review)
Review
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive hematologic malignancy linked to HTLV-1 infection, which is refractory to therapy. The precise mechanism of oncogenesis in ATLL is incompletely understood, however, oncogenic viral genes Tax and Hbz are implicated, and recent large genomic and transcriptome studies provide further insight. Despite progress in understanding the disease, survival and outcome with current therapies remain poor. Long-term survivors are reported, primarily among those with indolent disease or activating CC chemokine receptor 4 mutations, however, allogeneic hematopoietic stem cell transplant is the only curative treatment option. The majority of patients succumb to their disease and ongoing and collaborative research efforts are needed. I will review recent updates in HTLV-1-associated ATLL epidemiology, pathogenesis, therapy, and prevention.
Topics: Adult; Humans; Leukemia-Lymphoma, Adult T-Cell; Human T-lymphotropic virus 1; Gene Products, tax; HTLV-I Infections; Lymphoma
PubMed: 36584476
DOI: 10.1016/j.coviro.2022.101289 -
Viruses Jul 2022Human T cell leukemia virus type 1 (HTLV-1), the etiological agent of adult T cell leukemia/lymphoma (ATLL) and of HTLV-1-associated myelopathy/tropical spastic... (Review)
Review
Human T cell leukemia virus type 1 (HTLV-1), the etiological agent of adult T cell leukemia/lymphoma (ATLL) and of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), was identified a few years before Human Immunodeficiency Virus (HIV). However, forty years later, our comprehension of HTLV-1 immune detection and the host immune responses to HTLV-1 is far more limited than for HIV. In addition to innate and adaptive immune responses that rely on specialized cells of the immune system, host cells may also express a range of antiviral factors that inhibit viral replication at different stages of the cycle, in a cell-autonomous manner. Multiple antiviral factors allowing such an intrinsic immunity have been primarily and extensively described in the context HIV infection. Here, we provide an overview of whether known HIV restriction factors might act on HTLV-1 replication. Interestingly, many of them do not exert any antiviral activity against HTLV-1, and we discuss viral replication cycle specificities that could account for these differences. Finally, we highlight future research directions that could help to identify antiviral factors specific to HTLV-1.
Topics: Adult; Antiviral Agents; HIV Infections; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Paraparesis, Tropical Spastic
PubMed: 35893677
DOI: 10.3390/v14081611 -
Frontiers in Public Health 2022To perform a systematic review to describe the available findings on clinical outcomes in HIV-1 and HTLV-1/HTLV-2 co-infected individuals since 1995.
AIM
To perform a systematic review to describe the available findings on clinical outcomes in HIV-1 and HTLV-1/HTLV-2 co-infected individuals since 1995.
DESIGN
This Systematic Review used PECO criteria follow by PRISMA reporting guidelines and registered as CRD42021279062 (Prospero database). The Newcastle-Ottawa Scale assessed the methodological quality of included studies.
DATA COLLECTION AND ANALYSIS
A systematical search in PubMed/MEDLINE, Embase, Web of Sciences databases for cross-sectional, case-control, or cohort studies design to identify clinical and laboratorial outcomes related to HIV-1 and HTLV-1/2 coinfection. Search strategy: [("HIV-1" AND "HTLV-1" OR "HTLV-2") AND ("Coinfection") AND (1990/01/01:2021/12/31[Date- Publication])].
RESULTS
A total of 15 articles were included on this systematic review describing data of 2,566 mono and coinfected patients, 58% male, with mean age was 35.7 ± 5.7 years. HIV-1 and HTLV-1 coinfected patients were more likely to had shorter survival and faster progression to death or mortality than monoinfected ones. Coinfected had higher CD4 cell counts and less likelihood of ART use. In addition, higher frequency of diseases like ichthyosis (22.2 vs. 6.8%), scabies (18.6 vs. 0%), candidiasis (42 vs. 12%), Strongyloidiasis (15.4 vs. 2%) and neurological manifestations like encephalopathy, peripheral neuropathy and HAM/TSP were more frequently reported in coinfected patients.
CONCLUSIONS
HIV-1 and HTLV-1 coinfection and HIV-1 and HTLV-1 /2 triple coinfection were related to shorter survival, higher mortality rate, and faster progression to death, while coinfection by HIV-1/HTLV-2 seems to have neutral association with longer survival, slower AIDS progression, and lower mortality rate. The available evidence indicates an urgent need for prevention and control measures, including screening, diagnosis, and treatment of HIV-1 and HTLV-1/2 coinfected patients. Test-and-treat strategy for patients living with HIV in areas endemic for HTLV infection is mandatory, to avoid the risks of delayed therapy and death for coinfected patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42021279062.
Topics: Adult; Coinfection; Cross-Sectional Studies; Female; HIV Infections; HIV-1; HTLV-I Infections; HTLV-II Infections; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Humans; Male
PubMed: 35359787
DOI: 10.3389/fpubh.2022.820727 -
Retrovirology Sep 2019Of the members of the primate T cell lymphotropic virus (PTLV) family, only the human T-cell leukemia virus type-1 (HTLV-1) causes disease in humans-as the etiological... (Review)
Review
Of the members of the primate T cell lymphotropic virus (PTLV) family, only the human T-cell leukemia virus type-1 (HTLV-1) causes disease in humans-as the etiological agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other auto-inflammatory disorders. Despite having significant genomic organizational and structural similarities, the closely related human T-cell lymphotropic virus type-2 (HTLV-2) is considered apathogenic and has been linked with benign lymphoproliferation and mild neurological symptoms in certain infected patients. The silencing of proviral gene expression and maintenance of latency are central for the establishment of persistent infections in vivo. The conserved pX sequences of HTLV-1 and HTLV-2 encode several ancillary factors which have been shown to negatively regulate proviral gene expression, while simultaneously activating host cellular proliferative and pro-survival pathways. In particular, the ORF-II proteins, HTLV-1 p30 and HTLV-2 p28, suppress Tax-dependent transactivation from the viral promoter-whereas p30 also inhibits PU.1-mediated inflammatory-signaling, differentially augments the expression of p53-regulated metabolic/pro-survival genes, and induces lymphoproliferation which could promote mitotic proviral replication. The ubiquitinated form of the HTLV-1 p13 protein localizes to nuclear speckles and interferes with recruitment of the p300 coactivator by the viral transactivator Tax. Further, the antisense-encoded HTLV-1 HBZ and HTLV-2 APH-2 proteins and mRNAs negatively regulate Tax-dependent proviral gene expression and activate inflammatory signaling associated with enhanced T-cell lymphoproliferation. This review will summarize our current understanding of the pX latency-maintenance factors of HTLV-1 and HTLV-2 and discuss how these products may contribute to the differences in pathogenicity between the human PTLVs.
Topics: Gene Expression Regulation, Viral; HTLV-I Infections; HTLV-II Infections; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Humans; Primate T-lymphotropic virus 1; Retroviridae Proteins, Oncogenic; Transcription Factors; Viral Regulatory and Accessory Proteins; Virus Latency
PubMed: 31492165
DOI: 10.1186/s12977-019-0487-9 -
Viruses Nov 2021Paradigm shifts throughout the history of microbiology have typically been ignored, or met with skepticism and resistance, by the scientific community. This has been... (Review)
Review
Paradigm shifts throughout the history of microbiology have typically been ignored, or met with skepticism and resistance, by the scientific community. This has been especially true in the field of virology, where the discovery of a "", or infectious fluid remaining after excluding bacteria by filtration, was initially ignored because it did not coincide with the established view of microorganisms. Subsequent studies on such infectious agents, eventually termed "viruses", were met with skepticism. However, after an abundance of proof accumulated, viruses were eventually acknowledged as defined microbiological entities. Next, the proposed role of viruses in oncogenesis in animals was disputed, as was the unique mechanism of genome replication by reverse transcription of RNA by the retroviruses. This same pattern of skepticism holds true for the prediction of the existence of retroviral "antisense" transcripts and genes. From the time of their discovery, it was thought that retroviruses encoded proteins on only one strand of proviral DNA. However, in 1988, it was predicted that human immunodeficiency virus type 1 (HIV-1), and other retroviruses, express an antisense protein encoded on the DNA strand opposite that encoding the known viral proteins. Confirmation came quickly with the characterization of the antisense protein, HBZ, of the human T-cell leukemia virus type 1 (HTLV-1), and the finding that both the protein and its antisense mRNA transcript play key roles in viral replication and pathogenesis. However, acceptance of the existence, and potential importance, of a corresponding antisense transcript and protein (ASP) in HIV-1 infection and pathogenesis has lagged, despite gradually accumulating theoretical and experimental evidence. The most striking theoretical evidence is the finding that is highly conserved in group M viruses and correlates exclusively with subtypes, or clades, responsible for the AIDS pandemic. This review outlines the history of the major shifts in thought pertaining to the nature and characteristics of viruses, and in particular retroviruses, and details the development of the hypothesis that retroviral antisense transcripts and genes exist. We conclude that there is a need to accelerate studies on ASP, and its transcript(s), with the view that both may be important, and overlooked, targets in anti-HIV therapeutic and vaccine strategies.
Topics: Carcinogenesis; Genome, Viral; HIV-1; History, 20th Century; History, 21st Century; Human Immunodeficiency Virus Proteins; Human T-lymphotropic virus 1; Humans; Open Reading Frames; RNA, Antisense; RNA, Messenger; Retroviridae; Retroviridae Proteins; Transcription, Genetic; Viral Envelope Proteins; Virology; Virus Replication
PubMed: 34835027
DOI: 10.3390/v13112221 -
Frontiers in Public Health 2022HTLV-1 is a retrovirus which causes diverse diseases in 10% of its infected population, significantly worsening their quality of life and mortality rate. Even though it...
HTLV-1 is a retrovirus which causes diverse diseases in 10% of its infected population, significantly worsening their quality of life and mortality rate. Even though it is globally distributed and is endemic in many countries (including Peru), it is still highly neglected. It spreads through vertical, sexual and parenteral transmission. As no effective treatment against this virus exist, prevention is required to contain it. The World Health Organization published a technical report on the matter in 2021, with the collaboration of international HTLV-1 experts. However, neither the impact of sexual transmission (cause of the majority of adult cases and infection in non-endemic areas) nor its prevention were considered. Evidence is presented, which shows the magnitude of sexual transmission, its risk factors and preventive measures; hoping it will encourage health workers to help eradicate this infection.
Topics: Adult; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Quality of Life; Risk Factors; Sexually Transmitted Diseases
PubMed: 35433594
DOI: 10.3389/fpubh.2022.840295 -
British Journal of Haematology Jan 2024Human T-cell leukaemia virus type 1 (HTLV-1) is a human retrovirus that causes adult T-cell lymphoma and HTLV-associated myelopathy. In this issue, Rosadas et al. use...
Human T-cell leukaemia virus type 1 (HTLV-1) is a human retrovirus that causes adult T-cell lymphoma and HTLV-associated myelopathy. In this issue, Rosadas et al. use data from a recent WHO report to describe how blood banks test for HTLV-1 and how this testing contributes to public health surveillance for the virus. Commentary on: Rosadas et al. HTLV-1 screening of blood donations: we are systematically missing opportunities. Br J Haematol 2023;202:1220-1223.
Topics: Adult; Humans; Human T-lymphotropic virus 1; Blood Donation; Leukemia-Lymphoma, Adult T-Cell; HTLV-I Infections
PubMed: 37575044
DOI: 10.1111/bjh.19051 -
Journal of Biomolecular Structure &... Sep 2022Human T cell leukemia virus type-1 (HTLV-1) is the cause of adult T cell leukemia/lymphoma (ATL), uveitis, and certain pulmonary diseases. In recent decades, many...
Human T cell leukemia virus type-1 (HTLV-1) is the cause of adult T cell leukemia/lymphoma (ATL), uveitis, and certain pulmonary diseases. In recent decades, many scientists have proposed the development of different treatment and prevention strategies to combat HTLV-1 infection. In this study, we used bioinformatics tools to predict peptide and protein vaccine candidates against HTLV-1 that can potentially induce antibody production and both CD4+ and CD8+ T cell immune responses. Five critical proteins, viz., , and analyzed for predicting immunogenic T and B cell epitopes and subsequently evaluated using bioinformatics tools. Based on the predictions, the most antigenic epitopes were selected, and their interaction with immune receptors was investigated. We also designed a protein vaccine candidate with an eight-epitopes-rich domain, including Then, the interaction of the epitope and the designed protein with immune receptors was validated in an docking study. The docking analysis showed that the O2 epitope and D8 protein interact strongly with immune receptors, especially the HLA-A*02:01 receptor. The stability of the interactions was investigated by molecular dynamics (MD) for 100 ns. The root mean square deviation, radius of gyration, hydrogen bonds, and solvent-accessible surface area were calculated for the 100 ns trajectory period. MD studies demonstrated that the O2-HLA-A*02:01 and D8-HLA-A*02:01 complexes were stable during the simulation. Analysis of results showed that the peptide and the designed protein could elicit humoral and cell-mediated immune responses.Communicated by Ramaswamy H. Sarma.
Topics: Adult; Epitopes, B-Lymphocyte; Epitopes, T-Lymphocyte; HLA-A Antigens; Human T-lymphotropic virus 1; Humans; Molecular Docking Simulation; Peptides; Vaccines; Vaccines, Subunit
PubMed: 33648421
DOI: 10.1080/07391102.2021.1889669 -
Scientific Reports Oct 2022Human T-lymphotropic viruses 1 and 2 (HTLV-1/2) have a worldwide distribution. HTLV-1 has been associated with several diseases, including an aggressive malignant...
Human T-lymphotropic viruses 1 and 2 (HTLV-1/2) have a worldwide distribution. HTLV-1 has been associated with several diseases, including an aggressive malignant disease known as adult T-cell leukemia/lymphoma and a chronic inflammatory neurological disease called HTLV-1-associated myelopathy, while HTLV-2 has not been definitively associated with diseases. HTLV-2 is most prevalent in specific groups such as injecting drug users and the indigenous population. In Brazil, most studies about HTLV in indigenous are carried out in indigenous communities from the north of the country. Mato Grosso do Sul (MS), Central Brazil, has the second-largest indigenous population in Brazil. However, there is no available data about HTLV infection in this group. We conducted the first investigation of HTLV-1/2 infection prevalence in the indigenous population from Jaguapiru and Bororó villages in Dourados City, MS, to provide the prevalence and molecular characterization of HTLV. For that, a total of 1875 indigenous participated in the study. All the serum samples were screened by an enzyme-linked immunosorbent assay commercial kit for the presence of anti-HTLV-1/2 antibodies. Positive samples were confirmed by HTLV-1/2 Western Blot assay. The HTLV-1 5'LTR region was detected by nested PCR amplification and sequenced by Sanger. Most of the study population declared belonging to Guarani-Kaiowá ethnicity (69.18%), 872 (46.51%), and 1003 (53.49%) were from Jaguapiru and Bororó villages, respectively. The median age of participants was 31 years, and 74.24% were females. Two individuals were detected with HTLV-1 (0.1%; CI 95% 0.1-0.2). The phylogenetic analysis revealed that isolates belong to the Cosmopolitan subtype and the Transcontinental subgroup (HTLV-1aA). The low HTLV-1 prevalence found in this study is similar to that observed among blood donors, and pregnant populations from Mato Grosso do Sul. The absence of HTLV-2 infection among these Brazilian indigenous communities would suggest a distinct behavior pattern from other indigenous populations in Brazil.
Topics: Adult; Brazil; Female; HTLV-I Infections; HTLV-II Infections; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Humans; Male; Phylogeny; Pregnancy; Prevalence
PubMed: 36202887
DOI: 10.1038/s41598-022-21086-7