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Search Results: 1 - 10 of 745 matches for " Renaud Mahieux "
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HTLV-3/STLV-3 and HTLV-4 Viruses: Discovery, Epidemiology, Serology and Molecular Aspects
Renaud Mahieux,Antoine Gessain
Viruses , 2011, DOI: 10.3390/v3071074
Abstract: Human T cell leukemia/lymphoma virus Type 1 and 2 (HTLV-1 and HTLV-2), together with their simian counterparts (STLV-1, STLV-2), belong to the Primate T lymphotropic viruses group (PTLV). The high percentage of homologies between HTLV-1 and STLV-1 strains, led to the demonstration that most HTLV-1 subtypes arose from interspecies transmission between monkeys and humans. STLV-3 viruses belong to the third PTLV type and are equally divergent from both HTLV-1 and HTLV-2. They are endemic in several monkey species that live in West, Central and East Africa. In 2005, we, and others reported the discovery of the human homolog (HTLV-3) of STLV-3 in two asymptomatic inhabitants from South Cameroon whose sera exhibited HTLV indeterminate serologies. More recently, two other cases of HTLV-3 infection in persons living in Cameroon were reported suggesting that this virus is not extremely rare in the human population living in Central Africa. Together with STLV-3, these human viral strains belong to the PTLV-3 group. A fourth HTLV type (HTLV-4) was also discovered in the same geographical area. The overall PTLV-3 and PTLV-4 genomic organization is similar to that of HTLV-1 and HTLV-2 with the exception of their long terminal repeats (LTRs) that contain only two 21 bp repeats. As in HTLV-1, HTLV-3 Tax contains a PDZ binding motif while HTLV-4 does not. An antisense transcript was also described in HTLV-3 transfected cells. PTLV-3 molecular clones are now available and will allow scientists to study the viral cycle, the tropism and the possible pathogenicity in vivo. Current studies are also aimed at determining the prevalence, distribution, and modes of transmission of these viruses, as well as their possible association with human diseases. Here we will review the characteristics of these new simian and human retroviruses, whose discovery has opened new avenues of research in the retrovirology field.
HTLV-1 and Innate Immunity
Chloé Journo,Renaud Mahieux
Viruses , 2011, DOI: 10.3390/v3081374
Abstract: Innate immunity plays a critical role in the host response to a viral infection. The innate response has two main functions. First, it triggers effector mechanisms that restrict the infection. Second, it primes development of the adaptive response, which completes the elimination of the pathogen or of infected cells. In vivo, HTLV-1 infects T lymphocytes that participate in adaptive immunity but also monocytes and dendritic cells that are major players in innate immunity. Herein, we will review the interplay between HTLV-1 and innate immunity. Particular emphasis is put on HTLV-1-induced alteration of type-I interferon (IFN-I) function. In vitro, the viral Tax protein plays a significant role in the alteration of IFN synthesis and signaling. Despite this, IFN-I/AZT treatment of Adult T?cell Leukemia/Lymphoma (ATLL) patients leads to complete remission. We will discuss a model in which exogenous IFN-I could act both on the microenvironment of the T-cells to protect them from infection, and also on infected cells when combined with other drugs that lead to Tax down-regulation/degradation.
Centrosome and retroviruses: The dangerous liaisons
Philippe V Afonso, Alessia Zamborlini, Ali Sa?b, Renaud Mahieux
Retrovirology , 2007, DOI: 10.1186/1742-4690-4-27
Abstract: Centrosomes were first described at the end of the 19th century by Theodor Boveri who had also the intuition of their central role in cell life [1].Centrosomes are animal-specific non-membranous organelles that localize in close proximity to the cell nucleus for the duration of interphase. Their structure is highly conserved among higher eukaryotes. It usually consists of a pair of centrioles joined by fibers connecting their proximal ends which are embedded into a protein-dense matrix called the pericentriolar material (PCM) [2,3]. The PCM is an ordered lattice that anchors a large number of microtubule (MT)-associated proteins, many of which bear putative coiled-coil domains, a tertiary structure known to facilitate protein-protein interactions [4]. Centrioles are cylindrical corps formed by a radial array of nine MT-triplets, which are structurally similar to basal bodies of eukaryotic cilia and flagella [5,6]. Centrioles play a role in the organization of the microtubular cytoskeleton, but they do not make direct contact with the MTs which nucleate from the γ-tubulin ring complexes (γ-TuRC) located within the PCM.In animal cells, centrosomes represent the major microtubule-organizing structures (MTOC). The MTOC is responsible to direct the assembly and the orientation of MTs and to control MT-dependent processes such as trafficking of cytoplasmic vesicles and orientation of cellular organelles. At the onset of mitosis, centrosomes become the core structures of spindle poles and direct the formation of mitotic spindles. Upon cytokinesis, each daughter cell receives only one centriole, which duplicates once per cell cycle.The number of centrosomes within a cell is strictly controlled [5] (Figure 1). In G1 phase, cells have a single centrosome consisting of two centrioles joined by cohesion fibers. At the G1/S transition, new centrioles grow orthogonally from each of the two pre-existing ones. They will elongate until G2, maintaining the strictly perpendicular conf
Discovery of a new human T-cell lymphotropic virus (HTLV-3) in Central Africa
Sara Calattini, Sébastien Chevalier, Renan Duprez, Sylviane Bassot, Alain Froment, Renaud Mahieux, Antoine Gessain
Retrovirology , 2005, DOI: 10.1186/1742-4690-2-30
Abstract: Three types of Primate T-cell lymphotropic viruses (PTLVs) have been discovered so far in primates [1]. While two of them i.e. PTLV-1 and PTLV-2 include human (HTLV-1, HTLV-2) and simian (STLV-1, STLV-2) viruses, the third type (STLV-3) consists only, so far, of simian strains. Sequence comparisons of STLV-3 proviruses indicated that these strains are highly divergent from HTLV-1 (60% nucleotide similarity), HTLV-2 (62%), or STLV-2 (62%) prototype sequences. In all phylogenetic analyses, STLV-3 viruses cluster in a highly supported group, indicating an evolutionary lineage independent from PTLV-1 and PTLV-2. Nevertheless, STLV-3 lineage is composed of at least three subtypes that are corresponding more or less to the geographical origin of the virus (East, West or Central Africa) [2-9]. Most of the viruses belonging to the PTLV-1 type cannot be separated into distinct phylogenetic lineages according to their species of origin. Their intermixing has therefore been inferred as an evidence for past or recent interspecies transmission episodes. The hypothesis of viral transmission from monkeys to humans is supported by an increasing number of observations [1]. Thus, it has been proposed that HTLV strains related to STLV-3 might infect human populations living in areas where STLV-3 is present.Cameroon has a remarkable diversity of retroviruses. All the subtypes of HIV-1 group M (A to H) are present, subtype-recombinant strains co-circulate, and HIV-1 groups O and N have been reported. Besides, HTLV-1 subtypes B and D as well as HTLV-2 type A and B are also present in Cameroonian individuals, while STLV-1 and STLV-3 strains have been isolated from several non-human primates (NHPs) species living in this region [3,4,8]. We therefore conducted a study to search for HTLV variants in Cameroonian individuals with HTLV-1/2 indeterminate serology. This survey was approved by both the national (Cameroon Ministry of Health and their National Ethics committee) and local authorities
Presence of a functional but dispensable Nuclear Export Signal in the HTLV-2 Tax protein
Sébastien A Chevalier, Laurent Meertens, Sara Calattini, Antoine Gessain, Lars Kiemer, Renaud Mahieux
Retrovirology , 2005, DOI: 10.1186/1742-4690-2-70
Abstract: We first used a NES prediction method to determine whether the Tax2 protein might contain a NES and the results do suggest the presence of a NES sequence in Tax2. Using Green Fluorescent Protein-NES (GFP-NES) fusion proteins, we demonstrate that the Tax2 sequence encompasses a functional NES (NES2). As shown by microscope imaging, NES2 is able to mediate translocation of GFP from the nucleus, without the context of a full length Tax protein. Furthermore, point mutations or leptomycin B treatment abrogate NES2 function. However, within the context of full length Tax2, similar point mutations in the NES2 leucine rich stretch do not modify Tax2 localization. Finally, we also show that Tax1 NES function is dependent upon the positioning of the nuclear export signal "vis-à-vis" GFP.HTLV-2 Tax NES is functional but dispensable for the protein localization in vitro.HTLV-1 and HTLV-2 are closely related retroviruses that infect T-cells in vivo, with a probable preferential tropism for CD4+ and CD8+ cells respectively [1]. HTLV-1 is the etiological agent of the Adult T-cell Leukemia/Lymphoma (ATLL) and of the Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM), while HTLV-2 infection, even if originally described in a patient suffering of atypical hairy T-cell leukemia, has only been linked to infrequent cases of TSP/HAM "like" disease [2-4]. Both HTLV-1 and HTLV-2 genomes encode a viral transactivator (Tax1 and Tax2 respectively). Tax1 has an oncogenic potential and is responsible for cell-transformation in vitro [5,6]. Tax1 and Tax2 display approximately 75% nucleotide sequence homology. Strikingly however, several reports have now demonstrated that although the critical functional regions of the proteins are well conserved (i.e. NF-κB and CREB/ATF activation domains), the two transactivators exhibit a number of major phenotypical differences [1,7-18]. Nevertheless, Tax2 is capable of immortalizing human lymphocytes and, although to a lesser extent than Tax
Conference highlights of the 15th international conference on human retrovirology: HTLV and related retroviruses, 4-8 june 2011, Leuven, Gembloux, Belgium
Fabiola Martin, Charles RM Bangham, Vincenzo Ciminale, Michael D Lairmore, Edward L Murphy, William M Switzer, Renaud Mahieux
Retrovirology , 2011, DOI: 10.1186/1742-4690-8-86
Abstract: The biannual Conference on Human Retrovirology: HTLV and Related Viruses, where 325 delegated from 17 countries gathered, was held in Leuven, Belgium in June 2011. Two hundred and sixty one abstracts were submitted, and those accepted divided into 77 oral and 184 poster presentations. All abstracts can be viewed online: http://htlv.net webcite and http://www.retrovirology.com/supplements webcite. Experts in seven fields of retrovirology were asked to write summaries and comments on the most intriguing novel data and share their views on future research directions. During the meeting, Professor K.T. Jeang received the The Dale McFarlin Prize, Professor L. Willems was awarded with the HTLV Retrovirology Prize and the Young Scientists Awards went to A. Desrames, J. Turpin and C. Hhela.The human T-lymphotropic virus type 1 (HTLV-1) retrovirus infects 15 to 20 millions individuals throughout the world. HTLV-1 antibody prevalence rate varies from 0.2 to 10% among adults, depending on the geographical area. It increases with age, in some places eventually reaching 20 to 50% of the female population aged 60 and above. The two major diseases associated with HTLV-1 are Adult T-cell Leukemia/Lymphoma or ATLL and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis or HAM/TSP [1]. Xenotropic Murine Leukemia virus-Related Virus (XMRV) was identified in 2006 in stromal cells associated with prostate cancers [2] and later in patients suffering from chronic fatigue syndrome. The etiological role of XMRV in these two diseases has recently been challenged. Bovine Leukemia virus (BLV) infects B-lymphocytes and cause B leukemia [3]. Foamy viruses infect a wide number of animal species, as well as humans, but do not cause any disease [4].Two studies used the blood bank setting to measure HTLV prevalence on a large scale. A study from the United States of America [5] included all first-time blood donors at a large blood bank network over a ten-year period from 2000 through 2009. Amo
The Transcription Profile of Tax-3 Is More Similar to Tax-1 than Tax-2: Insights into HTLV-3 Potential Leukemogenic Properties
Sébastien A. Chevalier, Stéphanie Durand, Arindam Dasgupta, Michael Radonovich, Andrea Cimarelli, John N. Brady, Renaud Mahieux, Cynthia A. Pise-Masison
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0041003
Abstract: Human T-cell Lymphotropic Viruses type 1 (HTLV-1) is the etiological agent of Adult T-cell Leukemia/Lymphoma. Although associated with lymphocytosis, HTLV-2 infection is not associated with any malignant hematological disease. Similarly, no infection-related symptom has been detected in HTLV-3-infected individuals studied so far. Differences in individual Tax transcriptional activity might account for these distinct physiopathological outcomes. Tax-1 and Tax-3 possess a PDZ binding motif in their sequence. Interestingly, this motif, which is critical for Tax-1 transforming activity, is absent from Tax-2. We used the DNA microarray technology to analyze and compare the global gene expression profiles of different T- and non T-cell types expressing Tax-1, Tax-2 or Tax-3 viral transactivators. In a T-cell line, this analysis allowed us to identify 48 genes whose expression is commonly affected by all Tax proteins and are hence characteristic of the HTLV infection, independently of the virus type. Importantly, we also identified a subset of genes (n = 70) which are specifically up-regulated by Tax-1 and Tax-3, while Tax-1 and Tax-2 shared only 1 gene and Tax-2 and Tax-3 shared 8 genes. These results demonstrate that Tax-3 and Tax-1 are closely related in terms of cellular gene deregulation. Analysis of the molecular interactions existing between those Tax-1/Tax-3 deregulated genes then allowed us to highlight biological networks of genes characteristic of HTLV-1 and HTLV-3 infection. The majority of those up-regulated genes are functionally linked in biological processes characteristic of HTLV-1-infected T-cells expressing Tax such as regulation of transcription and apoptosis, activation of the NF-κB cascade, T-cell mediated immunity and induction of cell proliferation and differentiation. In conclusion, our results demonstrate for the first time that, in T- and non T-cells types, Tax-3 is a functional analogue of Tax-1 in terms of transcriptional activation and suggest that HTLV-3 might share pathogenic features with HTLV-1 in vivo.
Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery
Rachel Van Duyne, Irene Guendel, Zachary Klase, Aarthi Narayanan, William Coley, Elizabeth Jaworski, Jessica Roman, Anastas Popratiloff, Renaud Mahieux, Kylene Kehn-Hall, Fatah Kashanchi
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040662
Abstract: The innate ability of the human cell to silence endogenous retroviruses through RNA sequences encoding microRNAs, suggests that the cellular RNAi machinery is a major means by which the host mounts a defense response against present day retroviruses. Indeed, cellular miRNAs target and hybridize to specific sequences of both HTLV-1 and HIV-1 viral transcripts. However, much like the variety of host immune responses to retroviral infection, the virus itself contains mechanisms that assist in the evasion of viral inhibition through control of the cellular RNAi pathway. Retroviruses can hijack both the enzymatic and catalytic components of the RNAi pathway, in some cases to produce novel viral miRNAs that can either assist in active viral infection or promote a latent state. Here, we show that HTLV-1 Tax contributes to the dysregulation of the RNAi pathway by altering the expression of key components of this pathway. A survey of uninfected and HTLV-1 infected cells revealed that Drosha protein is present at lower levels in all HTLV-1 infected cell lines and in infected primary cells, while other components such as DGCR8 were not dramatically altered. We show colocalization of Tax and Drosha in the nucleus in vitro as well as coimmunoprecipitation in the presence of proteasome inhibitors, indicating that Tax interacts with Drosha and may target it to specific areas of the cell, namely, the proteasome. In the presence of Tax we observed a prevention of primary miRNA cleavage by Drosha. Finally, the changes in cellular miRNA expression in HTLV-1 infected cells can be mimicked by the add back of Drosha or the addition of antagomiRs against the cellular miRNAs which are downregulated by the virus.
Direct Detection of Diverse Metabolic Changes in Virally Transformed and Tax-Expressing Cells by Mass Spectrometry
Prabhakar Sripadi,Bindesh Shrestha,Rebecca L. Easley,Lawrence Carpio,Kylene Kehn-Hall,Sebastien Chevalier,Renaud Mahieux,Fatah Kashanchi,Akos Vertes
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012590
Abstract: Viral transformation of a cell starts at the genetic level, followed by changes in the proteome and the metabolome of the host. There is limited information on the broad metabolic changes in HTLV transformed cells.
Anti-HTLV antibody profiling reveals an antibody signature for HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)
Peter D Burbelo, Elise Meoli, Hannah P Leahy, Jhanelle Graham, Karen Yao, Unsong Oh, John E Janik, Renaud Mahieux, Fatah Kashanchi, Michael J Iadarola, Steven Jacobson
Retrovirology , 2008, DOI: 10.1186/1742-4690-5-96
Abstract: Anti-GAG antibody titers detected by LIPS differentiated HTLV-infected subjects from uninfected controls with 100% sensitivity and 100% specificity, but did not differ between HTLV-I infected subgroups. However, anti-Env antibody titers were over 4-fold higher in HAM/TSP compared to both asymptomatic HTLV-I (P < 0.0001) and ATLL patients (P < 0.0005). Anti-Env antibody titers above 100,000 LU had 75% positive predictive value and 79% negative predictive value for identifying the HAM/TSP sub-type. Anti-Tax antibody titers were also higher (P < 0.0005) in the HAM/TSP compared to the asymptomatic HTLV-I carriers. Proviral load correlated with anti-Env antibodies in asymptomatic carriers (R = 0.76), but not in HAM/TSP.These studies indicate that anti-HTLV-I antibody responses detected by LIPS are useful for diagnosis and suggest that elevated anti-Env antibodies are a common feature found in HAM/TSP patients.Human T lymphotropic virus type I (HTLV-I) is a retrovirus that infects 20 million people worldwide [1]. HTLV-I infection can cause a variety of human diseases including adult T-cell leukemia/lymphoma (ATLL) [2-4], HTLV-I associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) [5], infective dermatitis [6], and uveitis [7]. While the two major HTLV-I-associated diseases, ATLL and HAM/TSP, are present in all endemic areas, including Japan, the Caribbean basin, South America and parts of Africa, the incidence rates show geographic heterogeneity [1]. ATLL is an aggressive monoclonal proliferation of HTLV-1 infected CD4+ T cells that occurs mostly in adults. Perinatal HTLV-I infection is thought to be associated with a heightened risk of developing ATLL after a long latency period. Although the pathogenesis of ATLL is not completely understood, the HTLV-I regulatory protein Tax plays a critical role in cellular transformation by interfering with genome instability, cell cycle and apoptosis [8].HAM/TSP is a chronic progressive neurodegenerative disorder that involve
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