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Journal of Medical Virology Sep 2023Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that causes adult T-cell leukemia/lymphoma (ATL). HTLV-1 encodes Tax protein that activates...
Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that causes adult T-cell leukemia/lymphoma (ATL). HTLV-1 encodes Tax protein that activates transcription from viral long terminal repeats (LTR). Multiple cofactors are involved in the regulation of HTLV-1 transcription via association with Tax. Yes-associated protein (YAP), which is the key effector of Hippo pathway, is elevated and activated in ATL cells. In this study, we reported that YAP protein suppressed Tax activation of HTLV-1 5' LTR but not 3' LTR. The activation of the 5' LTR by Tax was potentiated when YAP was depleted. Moreover, overexpression of YAP repressed HTLV-1 plus-strand viral gene expression and virion production, whereas compromising YAP by RNA inference augmented the expression of HTLV-1 protein. As mechanisms of YAP-mediated viral transcription inhibition, we found that YAP interacted with Tax, and prevented the association between Tax and p300. It finally led to the inhibition of recruitment of Tax to the Tax-responsive element in the 5' LTR of HTLV-1. Taken together, our results demonstrate the negative regulatory function of YAP in Tax activation of HTLV-1 transcription. It may achieve sufficient transcriptional repression to maintain persistent infection and long-term latency of HTLV-1 in the host cells.
Topics: Adult; Humans; Human T-lymphotropic virus 1; Gene Expression; Persistent Infection; RNA; Leukemia, T-Cell
PubMed: 37661566
DOI: 10.1002/jmv.29065 -
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 -
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 -
MSphere Sep 2020Bats are the reservoir for a large number of zoonotic viruses, including members of (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARS-CoV-2), (Hendra...
Bats are the reservoir for a large number of zoonotic viruses, including members of (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARS-CoV-2), (Hendra and Nipah viruses), (rabies virus), and (Ebola virus) as exemplars. Many retroviruses, such as human immunodeficiency virus, are similarly zoonotic; however, only infectious exogenous gammaretroviruses have recently been identified in bats. Here, viral metagenomic sequencing of samples from bats submitted for rabies virus testing, largely due to human exposure, identified a novel, highly divergent exogenous from a big brown bat () in South Dakota. The virus sequence, corresponding to deltaretrovirus (EfDRV), comprised a nearly complete coding region comprised of canonical 5'-----3' genes with 37% to 51% identity to human T-lymphotropic virus (HTLV), an infectious retrovirus that causes T-cell lymphoma. A putative gene with 27% identity to HTLV was located downstream of the gene along with a gene harbored in an alternative reading frame which possessed a conserved domain for an Epstein-Barr virus nuclear antigen involved in gene transactivation, suggesting a regulatory function similar to that of the deltaretrovirus gene. A TaqMan reverse transcriptase PCR (RT-PCR) targeting the gene identified 4/60 (6.7%) bats as positive for EfDRV, which, combined with a search of the genome that failed to identify sequences with homology to EfDRV, suggests that EfDRV is an infectious exogenous virus. As all known members of can cause malignancies and is widely distributed in the Americas, often with a colonial roosting behavior in human dwellings, further studies are needed to investigate potential zoonosis. Bats host a large numbers of viruses, many of which are zoonotic. In the United States, the big brown bat () is widely distributed and lives in small colonies that roost in cavities, often in human dwellings, leading to frequent human interaction. Viral metagenomic sequencing of samples from an bat submitted for rabies testing identified the first exogenous bat The deltaretrovirus (EfDRV) genome consists of the typical deltaretrovial 5'-----3' genes along with genes encoding two putative transcriptional transactivator proteins distantly related to the Tax protein of human T-cell lymphotrophic virus and nuclear antigen 3B of Epstein-Barr virus. Searches of the genome sequence failed to identify endogenous EfDRV. RT-PCR targeting the EfDRV gene identified 4/60 (6.7%) bats with positive results. Together, these results suggest that EfDRV is exogenous. As all members of are associated with T- and B-cell malignancies or neurologic disease, further studies on possible zoonosis are warranted.
Topics: Animals; Chiroptera; Deltaretrovirus; Gene Products, tax; Genome, Viral; Humans; RNA, Viral; South Dakota; United States; Zoonoses
PubMed: 32968009
DOI: 10.1128/mSphere.00902-20 -
Seminars in Diagnostic Pathology Mar 2020Human T cell leukemia virus type 1 (HTLV-1) is a horizontally transmitted virus infection of CD4+ lymphocytes which causes adult T cell leukemia-lymphoma (ATLL) and... (Review)
Review
Human T cell leukemia virus type 1 (HTLV-1) is a horizontally transmitted virus infection of CD4+ lymphocytes which causes adult T cell leukemia-lymphoma (ATLL) and HTLV-associated myelopathy (HAM). The viral genome encodes two oncoproteins, transactivator protein (Tax) and helix basic zipper protein (HBZ), which are considered tumor initiator and maintenance factors, respectively. Tax is the primary inducer of clonal infected T cell expansion, and genetic instability. The immune response to Tax results in the selection of cells with little or no Tax expression, which have undergone genetic and epigenetic alterations that promote T cell activation, proliferation, and resistance to apoptosis. This selection of malignant cells occurs over several decades in 5% of infected individuals. Novel insights into the molecular details of each of these events has led to targeted therapies for ATLL.
Topics: Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell
PubMed: 31103249
DOI: 10.1053/j.semdp.2019.04.003 -
Frontiers in Immunology 2022Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus which mainly infects CD4 T cells and causes adult T-cell leukemia/lymphoma (ATL), is primarily transmitted... (Review)
Review
Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus which mainly infects CD4 T cells and causes adult T-cell leukemia/lymphoma (ATL), is primarily transmitted direct cell-to-cell transmission. This feature generates a wide variety of infected clones in hosts, which are maintained clonal proliferation, resulting in the persistence and survival of the virus. The maintenance of the pool of infected cells is achieved by sculpting the immunophenotype of infected cells and modulating host immune responses to avoid immune surveillance. Here, we review the processes undertaken by HTLV-1 to modulate and subvert host immune responses which contributes to viral persistence and development of ATL.
Topics: Adult; Humans; Human T-lymphotropic virus 1; Leukemia-Lymphoma, Adult T-Cell; Carcinogenesis; Immunophenotyping; T-Lymphocytes
PubMed: 36300109
DOI: 10.3389/fimmu.2022.991928