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PLoS Pathogens Apr 2022We investigated the impact of monocytes, NK cells, and CD8+ T-cells in primary HTLV-1 infection by depleting cell subsets and exposing macaques to either HTLV-1 wild...
We investigated the impact of monocytes, NK cells, and CD8+ T-cells in primary HTLV-1 infection by depleting cell subsets and exposing macaques to either HTLV-1 wild type (HTLV-1WT) or to the HTLV-1p12KO mutant unable to infect replete animals due to a single point mutation in orf-I that inhibits its expression. The orf-I encoded p8/p12 proteins counteract cytotoxic NK and CD8+ T-cells and favor viral DNA persistence in monocytes. Double NK and CD8+ T-cells or CD8 depletion alone accelerated seroconversion in all animals exposed to HTLV-1WT. In contrast, HTLV-1p12KO infectivity was fully restored only when NK cells were also depleted, demonstrating a critical role of NK cells in primary infection. Monocyte/macrophage depletion resulted in accelerated seroconversion in all animals exposed to HTLV-1WT, but antibody titers to the virus were low and not sustained. Seroconversion did not occur in most animals exposed to HTLV-1p12KO. In vitro experiments in human primary monocytes or THP-1 cells comparing HTLV-1WT and HTLV-1p12KO demonstrated that orf-I expression is associated with inhibition of inflammasome activation in primary cells, with increased CD47 "don't-eat-me" signal surface expression in virus infected cells and decreased monocyte engulfment of infected cells. Collectively, our data demonstrate a critical role for innate NK cells in primary infection and suggest a dual role of monocytes in primary infection. On one hand, orf-I expression increases the chances of viral transmission by sparing infected cells from efferocytosis, and on the other may protect the engulfed infected cells by modulating inflammasome activation. These data also suggest that, once infection is established, the stoichiometry of orf-I expression may contribute to the chronic inflammation observed in HTLV-1 infection by modulating monocyte efferocytosis.
Topics: Animals; HTLV-I Infections; Human T-lymphotropic virus 1; Inflammasomes; Killer Cells, Natural; Monocytes
PubMed: 35377924
DOI: 10.1371/journal.ppat.1010416 -
Proceedings of the National Academy of... Mar 2021HTLV-1-associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic...
HTLV-1-associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of , , , , , and genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in class I ( = 1.54 × 10) and class II ( = 1.21 × 10) loci with HAM/TSP. Association analysis using genotyping results showed that * ( = 2.61 × 10), * ( = 4.97 × 10), * ( = 1.15 × 10) and * ( = 2.30 × 10) were associated with disease risk, while * ( = 3.03 × 10), * ( = 1.06 × 10) and * ( = 1.78 × 10) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP ( = 9.52 × 10); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe.
Topics: Chromosome Mapping; Genome-Wide Association Study; HLA Antigens; Human T-lymphotropic virus 1; Humans; Japan; Paraparesis, Tropical Spastic; Polymorphism, Single Nucleotide; Viral Load
PubMed: 33649182
DOI: 10.1073/pnas.2004199118 -
Viruses Feb 2016Human T-cell Lymphotropic Virus type 1 (HTLV-1) is a human retrovirus that infects at least 5-10 million people worldwide, and is the etiological agent of a... (Review)
Review
Human T-cell Lymphotropic Virus type 1 (HTLV-1) is a human retrovirus that infects at least 5-10 million people worldwide, and is the etiological agent of a lymphoproliferative malignancy; Adult T-cell Leukemia/Lymphoma (ATLL); and a chronic neuromyelopathy, HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), as well as other inflammatory diseases such as infective dermatitis and uveitis. Besides sexual intercourse and intravenous transmission, HTLV-1 can also be transmitted from infected mother to child during prolonged breastfeeding. Some characteristics that are linked to mother-to-child transmission (MTCT) of HTLV-1, such as the role of proviral load, antibody titer of the infected mother, and duration of breastfeeding, have been elucidated; however, most of the mechanisms underlying HTLV-1 transmission during breast feeding remain largely unknown, such as the sites of infection and cellular targets as well as the role of milk factors. The present review focuses on the latest findings and current opinions and perspectives on MTCT of HTLV-1.
Topics: Adult; Female; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Infant; Infectious Disease Transmission, Vertical; Male
PubMed: 26848683
DOI: 10.3390/v8020040 -
Journal of Investigative Medicine High... 2021Adult T-cell leukemia/lymphoma is an aggressive T-cell malignancy caused by the long-term infection of human T-cell lymphotropic virus type 1 (HTLV-1). Our understanding...
Adult T-cell leukemia/lymphoma is an aggressive T-cell malignancy caused by the long-term infection of human T-cell lymphotropic virus type 1 (HTLV-1). Our understanding of clinical features still largely relies on the Shimoyama classification developed 30 years ago, which described the 4 clinical subtypes (the smoldering, chronic, lymphoma, and acute types) based on the manifestations of lymphocytosis, elevated lactate dehydrogenase, hypercalcemia, lymphadenopathy, and involvement of the skin, lung, liver, spleen, central nervous system, bone, ascites, pleural effusion, and gastrointestinal tract. HTLV-1-associated lymphoma has a variety of presentations but the presentation of massive lymphadenopathy and compression symptoms is rare and has not been emphasized in the literature. In this article, we describe 2 cases of adult T-cell leukemia/lymphomas that presented with massive cervical nodes or mediastinal nodes with compressing symptoms as the major presenting clinical features. Clinicians should remain aware of this type of presentation by HTLV-1-associated lymphoma, especially in patients who came from endemic areas, even if not all clinical features are present and particularly with hypercalcemia and lytic bone lesions.
Topics: Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Lymphadenopathy; Lymphoma; Skin
PubMed: 33969717
DOI: 10.1177/23247096211013235 -
Seminars in Diagnostic Pathology Mar 2020
Review
Topics: Eye Diseases; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Nervous System Diseases
PubMed: 31387754
DOI: 10.1053/j.semdp.2019.07.011 -
Preventive Veterinary Medicine Mar 2022A high herd and within-herd prevalence of Bovine Leukemia Virus (BLV) infections in the dairy herds of North America and the negative effects thereof caused the Alberta...
A high herd and within-herd prevalence of Bovine Leukemia Virus (BLV) infections in the dairy herds of North America and the negative effects thereof caused the Alberta dairy industry to initiate the development of an on farm BLV control program. Because BLV control is dependent on the commitment of the farmer, potential barriers were identified and farmers' and veterinarians' points of view toward different control options were investigated to inform how the control program might be adjusted. Conversations with these stakeholders were sought and four focus groups with farmers and eleven interviews with veterinarians were conducted. Testing for BLV, the most common BLV control strategies (testing/culling/segregation/management), as well as on farm best management practices (BMP) to prevent the transmission of BLV, were discussed. The thematic analysis of these conversations resulted in the following findings: Testing of animals was considered important for BLV control, but the financial investment was prohibitive for farmers. Test and cull as well as test and segregation approaches of test positive animals were considered efficient BLV control measures, but impractical and not feasible due to the supply managed Alberta dairy industry (i.e. milk is produced based on demand), with a high prevalence. The management of test positive animals with BMP to prevent new infections and thereby decreasing the within-herd prevalence was considered the only realistic BLV control strategy. The most important barriers for suggested BMP were the cost for some BMP, the inconvenience of performing other BMP, as well as difficulties in performing some BMP consistently and well. Additionally, a lack of knowledge about BLV and its control were identified as an important barrier. On the contrary, farmers indicated being inclined to implement BMP they considered feasible or that were considered a standard within the industry. Further, if BMP increased convenience on farm, they were considered easy to implement. Farmers and veterinarians agreed in many, but not all cases. For example, the single use of examination sleeves was met with differing opinions (i.e. considered doable by farmers while veterinarians assumed it to be too costly). In conclusion, stakeholders' awareness and communication amongst each other (e.g. veterinarians and farmers) about BLV and its control has to be highlighted in order to manage BLV infection successfully. In addition, by communicating and understanding barriers and motivators for specific BMP, important barriers could be identified (e.g. difficulties while changing needles), and solutions found (e.g. tool belt for needles), thereby improving BLV control efforts on farm.
Topics: Alberta; Animals; Dairying; Farmers; Humans; Leukemia Virus, Bovine; Veterinarians
PubMed: 35158251
DOI: 10.1016/j.prevetmed.2022.105590 -
Journal of the American Academy of... May 2023The Epstein-Barr virus (EBV) is a DNA virus that infects 90% of the human population, is responsible for certain cutaneous lymphomas (extranodal NK/T-cell lymhoma,... (Review)
Review
The Epstein-Barr virus (EBV) is a DNA virus that infects 90% of the human population, is responsible for certain cutaneous lymphomas (extranodal NK/T-cell lymhoma, hydroa vacciniforme lymphoproliferative disorder, lymphomatoid granulomatosis, others), and can be associated with a variety of cutaneous manifestations (eg, infectious mononucleosis, severe mosquito bite allergy, chronic active EBV disease, Gianotti-Crosti syndrome). EBV-related skin disorders are frequent in certain populations (South and Cental America, Africa, Asia, and Oceania) and can be diagnostically challenging. The human T-lymphotropic virus type-1 is a retrovirus, which is known to be associated with adult T-cell leukemia/lymphoma, neurologic disorders, but also cutaneous non-neoplastic manifestations (infective dermatitis, infections, and infestations). We performed an updated revision of the clinical dermatologic and histopathologic findings associated with the cutaneous non-neoplastic and preneoplastic disorders occurring in association with the EBV and human T-lymphotropic virus type-1.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Human T-lymphotropic virus 1; Skin; Lymphoproliferative Disorders
PubMed: 36049582
DOI: 10.1016/j.jaad.2022.07.063 -
Viruses Apr 2018Endogenous retrovirus (ERV) sequences provide a rich source of information about the long-term interactions between retroviruses and their hosts. However, most ERVs are...
Endogenous retrovirus (ERV) sequences provide a rich source of information about the long-term interactions between retroviruses and their hosts. However, most ERVs are derived from a subset of retrovirus groups, while ERVs derived from certain other groups remain extremely rare. In particular, only a single ERV sequence has been identified that shows evidence of being related to an ancient , despite the large number of vertebrate genome sequences now available. In this report, we identify a second example of an ERV sequence putatively derived from a past deltaretroviral infection, in the genomes of several species of horseshoe bats (Rhinolophidae). This sequence represents a fragment of viral genome derived from a single integration. The time of the integration was estimated to be 11-19 million years ago. This finding, together with the previously identified endogenous in long-fingered bats (Miniopteridae), suggest a close association of bats with ancient deltaretroviruses.
Topics: Animals; Chiroptera; Deltaretrovirus; Endogenous Retroviruses; Evolution, Molecular; Genome; Genomics; Phylogeny; Recombination, Genetic; Terminal Repeat Sequences
PubMed: 29642581
DOI: 10.3390/v10040185 -
Journal of Ocular Pharmacology and... May 2017Human T cell leukemia virus type 1, also known as human T lymphotropic virus type 1 (HTLV-1), is a retrovirus that encodes a reverse transcriptase, which translates... (Review)
Review
Human T cell leukemia virus type 1, also known as human T lymphotropic virus type 1 (HTLV-1), is a retrovirus that encodes a reverse transcriptase, which translates viral RNA into a DNA provirus that is integrated into the host genome. The virus was found to be a causative agent of adult T cell leukemia/lymphoma (ATL) in the early 1980s, and was also found to cause the neurological disorder tropical spastic paraparesis (TSP)/HTLV-1-associated myelopathy (HAM) and the inflammatory disorder HTLV-1 uveitis in the mid 1980s and early 1990s, respectively. This article reviews eye diseases caused by or related to HTLV-1: HTLV-1 uveitis, ocular and systemic complications of HTLV-1, keratoconjunctivitis sicca, interstitial keratitis, and ATL.
Topics: Eye Diseases; Human T-lymphotropic virus 1; Humans
PubMed: 28263674
DOI: 10.1089/jop.2016.0124 -
Retrovirology Feb 2024Human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV) have replicative and latent stages of infection. The status of the viruses is dependent on the... (Review)
Review
Human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV) have replicative and latent stages of infection. The status of the viruses is dependent on the cells that harbour them and on different events that change the transcriptional and post-transcriptional events. Non-coding (nc)RNAs are key factors in the regulation of retrovirus replication cycles. Notably, micro (mi)RNAs and long non-coding (lnc)RNAs are important regulators that can induce switches between active transcription-replication and latency of retroviruses and have important impacts on their pathogenesis. Here, we review the functions of miRNAs and lncRNAs in the context of HIV and HTLV. We describe how specific miRNAs and lncRNAs are involved in the regulation of the viruses' transcription, post-transcriptional regulation and latency. We further discuss treatment strategies using ncRNAs for HIV and HTLV long remission, reactivation or possible cure.
Topics: Humans; MicroRNAs; RNA, Long Noncoding; HIV; Gene Expression Regulation; RNA, Untranslated; Deltaretrovirus; Retroviridae; HIV Infections
PubMed: 38424561
DOI: 10.1186/s12977-024-00637-y