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Retrovirology Dec 2019Few years after HTLV-1 identification and isolation in humans, STLV-1, its simian counterpart, was discovered. It then became clear that STLV-1 is present almost in all... (Review)
Review
Few years after HTLV-1 identification and isolation in humans, STLV-1, its simian counterpart, was discovered. It then became clear that STLV-1 is present almost in all simian species. Subsequent molecular epidemiology studies demonstrated that, apart from HTLV-1 subtype A, all human subtypes have a simian homolog. As HTLV-1, STLV-1 is the etiological agent of ATL, while no case of TSP/HAM has been described. Given its similarities with HTLV-1, STLV-1 represents a unique tool used for performing clinical studies, vaccine studies as well as basic science.
Topics: Animals; Deltaretrovirus Infections; Disease Models, Animal; Female; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Male; Phylogeny; Primates; Simian T-lymphotropic virus 1
PubMed: 31843020
DOI: 10.1186/s12977-019-0503-0 -
Viruses Oct 2019Human T-lymphotropic virus 1, a member of the family, causes a neglected, silent, persistent infection affecting circa 5 to 10 million people around the world, with... (Review)
Review
Human T-lymphotropic virus 1, a member of the family, causes a neglected, silent, persistent infection affecting circa 5 to 10 million people around the world, with biology, immune pathology, clinical diseases, epidemiology, and laboratory issues still unsolved. Most of the infected subjects are asymptomatic, but severe clinical disorders appear as a neurodegenerative disease (HTLV-1 associated myelopathy-HAM) or a lymphoprolipherative disorder (Adult T Leukemia/Lymphoma-ATLL) and in other target organs of the human body. HTLV-1 infections are frequently asymptomatic, but there is a large spectrum of diseases that have been described along the years. The mechanisms by which the virus interacts with the host, the different modes of response of the host to the infection, and the immunogenic characteristics of the host are some of the interesting and unanswered questions that may direct the outcome of the disease. The most relevant published results dealing with the genetic variations of the host, the immune response to HTLV-1 infection, and the outcome of the infection are presented herein, including Human Leucocyte Antigen (HLA), Killer Immunoglobulin-like Receptors (KIR), interleukin 6, 10, 28, Fas and Fas ligand, IFN-gamma, TNF-A, and Mannose-binding lectin. In summary, there are still several unmet research needs in the field of useful biomarkers on HTLV-1 pathogenesis.
Topics: Animals; Biomarkers; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Immunogenetics
PubMed: 31652745
DOI: 10.3390/v11110974 -
The Brazilian Journal of Infectious... 2018Human T-lymphotropic viruses (HTLV) are Deltaretroviruses that infect millions of individuals worldwide via the same transmission routes as HIV. With the aim of exposing... (Review)
Review
Human T-lymphotropic viruses (HTLV) are Deltaretroviruses that infect millions of individuals worldwide via the same transmission routes as HIV. With the aim of exposing the possible re-emergence of HTLV in West Africa since discovery, a systematic review was carried out, focusing on the distribution of the virus types and significance of frequent indeterminate reports, while highlighting the need for mandatory routine blood screening. Capturing relevant data from discovery till date, sources searched were Google Scholar, CrossRef, NCBI (PubMed), MEDLINE, Research Gate, Mendeley, abstracts of Conferences and Proceedings, organization websites and reference lists of selected papers. A total of 2626 references were initially retrieved using search terms: Worldwide prevalence of HTLV, HTLV in Africa, HTLV in West Africa, HTLV subtypes, HTLV 3 and 4 in Africa, HTLV of African origin, HTLV seroindeterminate results, Spread of HTLV. These references were rigorously trimmed down to 76. Although evidence shows that HTLV is still endemic in the region, West Africa lacks recent epidemiological prevalence data. Thorough investigations are needed to ascertain the true cause of indeterminate Western Blot results. It is imperative that routine screening for HTLVs be mandated in West African health care facilities.
Topics: Africa, Western; Deltaretrovirus; Deltaretrovirus Infections; Female; Humans; Male; Prevalence; Risk Factors; Seroepidemiologic Studies
PubMed: 29879426
DOI: 10.1016/j.bjid.2018.05.003 -
Blood Dec 2016
Review
Topics: Donor Selection; Female; HTLV-II Infections; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Humans; Male; Paraparesis, Tropical Spastic
PubMed: 28034870
DOI: 10.1182/blood-2016-09-739433 -
Biomedicine & Pharmacotherapy =... Jan 2019Human T-cell lymphotropic virus type 1 (HTLV-1) infection is linked to adult T-cell leukemia-lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic... (Review)
Review
Human T-cell lymphotropic virus type 1 (HTLV-1) infection is linked to adult T-cell leukemia-lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and several other disorders. ATLL occurs in approximately 5% of the 15-20 million people infected by HTLV-1 in the world. In general, ATLL is resistant to chemotherapy, which underlines the need for new and effective therapeutic strategies. Previous studies highlighted the role of viral enzymes, responsible for viral replication, and regulatory proteins such as Tax and HBZ in the progression of HTLV-1-associated diseases. There are conflicting reports on the efficacy of current enzyme inhibitors, mainly developed against human immunodeficiency virus (HIV), for treatment of HTLV-1 infection. New treatment approaches including monoclonal antibodies show promising results and exert significant cytotoxic effects on ATLL cells. This manuscript reviews the recent developments in molecular targeting for treatment of HTLV-1 infection.
Topics: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Enzyme Inhibitors; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Molecular Targeted Therapy; Protein Structure, Secondary; Treatment Outcome
PubMed: 30551530
DOI: 10.1016/j.biopha.2018.10.139 -
Retrovirology Dec 2019The extraordinarily high prevalence of HTLV-1 subtype C (HTLV-1C) in some isolated indigenous communities in Oceania and the severity of the health conditions associated... (Review)
Review
The extraordinarily high prevalence of HTLV-1 subtype C (HTLV-1C) in some isolated indigenous communities in Oceania and the severity of the health conditions associated with the virus impress the great need for basic and translational research to prevent and treat HTLV-1 infection. The genome of the virus's most common subtype, HTLV-1A, encodes structural, enzymatic, and regulatory proteins that contribute to viral persistence and pathogenesis. Among these is the p30 protein encoded by the doubly spliced Tax-orf II mRNA, a nuclear/nucleolar protein with both transcriptional and post-transcriptional activity. The p30 protein inhibits the productive replication cycle via nuclear retention of the mRNA that encodes for both the viral transcriptional trans-activator Tax, and the Rex proteins that regulate the transport of incompletely spliced viral mRNA to the cytoplasm. In myeloid cells, p30 inhibits the PU-1 transcription factor that regulates interferon expression and is a critical mediator of innate and adaptive immunity. Furthermore, p30 alters gene expression, cell cycle progression, and DNA damage responses in T-cells, raising the hypothesis that p30 may directly contribute to T cell transformation. By fine-tuning viral expression while also inhibiting host innate responses, p30 is likely essential for viral infection and persistence. This concept is supported by the finding that macaques, a natural host for the closely genetically related simian T-cell leukemia virus 1 (STLV-1), exposed to an HTLV-1 knockout for p30 expression by a single point mutation do not became infected unless reversion and selection of the wild type HTLV-1 genotype occurs. All together, these data suggest that inhibition of p30 may help to curb and eventually eradicate viral infection by exposing infected cells to an effective host immune response.
Topics: Animals; Cell Line; Gene Expression; Gene Expression Regulation, Viral; Genotype; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Macaca; RNA, Viral; Retroviridae Proteins; Virus Latency
PubMed: 31852501
DOI: 10.1186/s12977-019-0501-2 -
The Lancet. Infectious Diseases Apr 2020
Topics: Epidemiologic Studies; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Outcome Assessment, Health Care
PubMed: 32222206
DOI: 10.1016/S1473-3099(20)30133-X -
The Lancet. Infectious Diseases Apr 2020
Topics: Epidemiologic Studies; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Outcome Assessment, Health Care
PubMed: 32222205
DOI: 10.1016/S1473-3099(20)30043-8 -
Biomedica : Revista Del Instituto... Mar 2022Individuals infected with the human T-lymphotropic virus type 1 (HTLV-1) may present severe and disseminated forms of Strongyloides stercoralis infection with low...
INTRODUCTION
Individuals infected with the human T-lymphotropic virus type 1 (HTLV-1) may present severe and disseminated forms of Strongyloides stercoralis infection with low therapeutic response.
OBJECTIVE
To investigate the S. stercoralis infection and the seroprevalence of IgG anti-S. stercoralis antibodies in individuals infected with HTLV-1 attending the Reference Center for HTLV-1 (CHTLV) in Salvador, Bahia, Brazil.
MATERIALS AND METHODS
We conducted a cross-sectional study in 178 HTLV-1-infected individuals treated at the HTLV specialized center between January, 2014, and December, 2018. The parasitological diagnosis of S. stercoralis was performed using the Hoffman, Pons and Janer, agar plate culture, and Baermann-Morais methods. The IgG anti-S. stercoralis detection was performed using an in house enzyme-linked immunosorbent assay (ELISA). The HTLV-1 infection was diagnosed using a commercial ELISA and confirmed by Western blot.
RESULTS
The frequency of S. stercoralis infection was 3.4% (6/178). Individuals infected with S. stercoralis from rural areas (50.0%; 3/6) also showed S. stercoralis hyperinfection (>3,000 larvae/gram of feces). The frequency of circulating anti-S. stercoralis IgG antibodies was 20.8% (37/178).
CONCLUSIONS
HTLV-1-infected people living in precarious sanitary conditions are more prone to develop severe forms of S. stercoralis infection. Considering the high susceptibility and unfavorable outcome of the infection in these individuals, the serological diagnosis for S. stercoralis should be considered when providing treatment.
Topics: Animals; Cross-Sectional Studies; Human T-lymphotropic virus 1; Humans; Immunoglobulin G; Seroepidemiologic Studies; Strongyloides stercoralis; Strongyloidiasis
PubMed: 35471168
DOI: 10.7705/biomedica.5888 -
Viruses Aug 2022The bovine leukemia virus (BLV) and the human T-lymphothropic viruses (HTLVs) are members of the deltaretrovirus genus of family. An essential event of the retroviral...
The bovine leukemia virus (BLV) and the human T-lymphothropic viruses (HTLVs) are members of the deltaretrovirus genus of family. An essential event of the retroviral life cycle is the processing of the polyproteins by the viral protease (PR); consequently, these enzymes became important therapeutic targets of the anti-retroviral drugs. As compared to human immunodeficiency viruses (HIVs), the deltaretroviruses have a different replication strategy, as they replicate predominantly in the DNA form, by forcing the infected cell to divide, unlike HIV-1, which replicates mainly by producing a vast number of progeny virions and by reinfection. Due to bypassing the error-prone reverse transcription step of replication, the PRs of deltaretroviruses did not undergo such extensive evolution as HIV PRs and remained more highly conserved. In this work, we studied the abilities of wild-type and modified BLV, HTLV (type 1, 2 and 3), and HIV-1 PRs (fused to an N-terminal MBP tag) for self-processing. We designed a cleavage site mutant MBP-fused BLV PR precursor as well, this recombinant enzyme was unable for self-proteolysis, the MBP fusion tag decreased its catalytic efficiency but showed an unusually low K for the IB-268 protease inhibitor. Our results show that the HTLV and BLV deltaretrovirus PRs exhibit lower mutation tolerance as compared to HIV-1 PR, and are less likely to retain their activity upon point mutations at various positions, indicating a higher flexibility of HIV-1 PR in tolerating mutations under selective pressure.
Topics: Deltaretrovirus; Endopeptidases; HIV Infections; HIV Protease; HIV Seropositivity; HIV-1; Humans; Leukemia Virus, Bovine; Mutation; Peptide Hydrolases; Polyproteins; Protease Inhibitors
PubMed: 36146695
DOI: 10.3390/v14091888