References of "Kettmann, Richard"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailThe transcription factor ERG recruits CCR4-NOT to control mRNA decay and mitotic progression.
Rambout, Xavier ULg; Detiffe, Cecile; Bruyr, Jonathan et al

in Nature Structural & Molecular Biology (2016)

Control of mRNA levels, a fundamental aspect in the regulation of gene expression, is achieved through a balance between mRNA synthesis and decay. E26-related gene (Erg) proteins are canonical ... [more ▼]

Control of mRNA levels, a fundamental aspect in the regulation of gene expression, is achieved through a balance between mRNA synthesis and decay. E26-related gene (Erg) proteins are canonical transcription factors whose previously described functions are confined to the control of mRNA synthesis. Here, we report that ERG also regulates gene expression by affecting mRNA stability and identify the molecular mechanisms underlying this function in human cells. ERG is recruited to mRNAs via interaction with the RNA-binding protein RBPMS, and it promotes mRNA decay by binding CNOT2, a component of the CCR4-NOT deadenylation complex. Transcriptome-wide mRNA stability analysis revealed that ERG controls the degradation of a subset of mRNAs highly connected to Aurora signaling, whose decay during S phase is necessary for mitotic progression. Our data indicate that control of gene expression by mammalian transcription factors may follow a more complex scheme than previously anticipated, integrating mRNA synthesis and degradation. [less ▲]

Detailed reference viewed: 42 (13 ULg)
Full Text
Peer Reviewed
See detailSystematic interactome mapping of acute lymphoblastic leukemia cancer gene products reveals EXT-1 tumor suppressor as a Notch1 and FBWX7 common interactor.
Daakour, Sarah ULg; Hajingabo, Leon Juvenal; Kerselidou, Despoina et al

in BMC Cancer (2016), 16(1), 335

BACKGROUND: Perturbed genotypes in cancer can now be identified by whole genome sequencing of large number of diverse tumor samples, and observed gene mutations can be used for prognosis and ... [more ▼]

BACKGROUND: Perturbed genotypes in cancer can now be identified by whole genome sequencing of large number of diverse tumor samples, and observed gene mutations can be used for prognosis and classification of cancer subtypes. Although mutations in a few causative genes are directly linked to key signaling pathways perturbation, a global understanding of how known cancer genes drive oncogenesis in human is difficult to assess. METHODS: We collected available information about mutated genes in Acute Lymphoblastic Leukemia (ALL). Validated human protein interactions (PPI) were collected from IntAct, HPRD and BioGRID interactomics databases, or obtained using yeast two-hybrid screening assay. RESULTS: We have mapped interconnections between 116 cancer census gene products associated with ALL. Combining protein-protein interactions data and cancer-specific gene mutations information, we observed that 63 ALL-gene products are interconnected and identified 37 human proteins interacting with at least 2 ALL-gene products. We highlighted exclusive and coexistence genetic alterations in key signaling pathways including the PI3K/AKT and the NOTCH pathways. We then used different cell lines and reporter assay systems to validate the involvement of EXT1 in the Notch pathway. CONCLUSION: We propose that novel ALL-gene candidates can be identified based on their functional association with well-known cancer genes. We identified EXT1, a gene not previously linked to ALL via mutations, as a common interactor of NOTCH1 and FBXW7 regulating the NOTCH pathway in an FBXW7-dependend manner. [less ▲]

Detailed reference viewed: 59 (7 ULg)
Full Text
Peer Reviewed
See detailInhibition of Tax transformation activity using a small molecule targetting Tax/PDZ domain interactions.
Blibek, Karim ULg; Fujii, Naoaki; Legros, Sebastien et al

Poster (2013, June 29)

Primate T-lymphotropic virus species comprise four members (HTLV-1 to -4) that have been discovered in human. Only the HTLV-1 infection leads to adult T-cell leukemia/lymphoma (ATLL) and tropical spastic ... [more ▼]

Primate T-lymphotropic virus species comprise four members (HTLV-1 to -4) that have been discovered in human. Only the HTLV-1 infection leads to adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis (TSP), an immune degenerative neurologic syndrome. All the four viruses share a similar genomic organization and encode transforming Tax oncoproteins. In contrast to HTLV-2 and 4, HTLV-1 and 3 Tax proteins contain a PSD-95/Drosophila Discs Large/Zona Occludens-I (PDZ) binding motif at their C-terminal that has been shown to play crucial roles in the distinct transforming properties of the Tax proteins. To systematically investigate PDZ-containing proteins roles in HTLV-1 biology, we initiated a global interactome network analysis of Tax and associated human PDZ-containing proteins. This was accomplished through the use of our framework of binary interactome mapping that includes stringent yeast two hybrid and pulldown screening, systematic retesting by protein complementation assay and evaluation of PDZ gene expression in T lymphocytes. [less ▲]

Detailed reference viewed: 54 (5 ULg)
Full Text
Peer Reviewed
See detailPP2A regulatory subunit Balpha controls endothelial contractility and vessel lumen integrity via regulation of HDAC7.
Martin, Maud ULg; Geudens, Ilse; Bruyr, Jonathan et al

in EMBO Journal (2013)

To supply tissues with nutrients and oxygen, the cardiovascular system forms a seamless, hierarchically branched, network of lumenized tubes. Here, we show that maintenance of patent vessel lumens ... [more ▼]

To supply tissues with nutrients and oxygen, the cardiovascular system forms a seamless, hierarchically branched, network of lumenized tubes. Here, we show that maintenance of patent vessel lumens requires the Balpha regulatory subunit of protein phosphatase 2A (PP2A). Deficiency of Balpha in zebrafish precludes vascular lumen stabilization resulting in perfusion defects. Similarly, inactivation of PP2A-Balpha in cultured ECs induces tubulogenesis failure due to alteration of cytoskeleton dynamics, actomyosin contractility and maturation of cell-extracellular matrix (ECM) contacts. Mechanistically, we show that PP2A-Balpha controls the activity of HDAC7, an essential transcriptional regulator of vascular stability. In the absence of PP2A-Balpha, transcriptional repression by HDAC7 is abrogated leading to enhanced expression of the cytoskeleton adaptor protein ArgBP2. ArgBP2 hyperactivates RhoA causing inadequate rearrangements of the EC actomyosin cytoskeleton. This study unravels the first specific role for a PP2A holoenzyme in development: the PP2A-Balpha/HDAC7/ArgBP2 axis maintains vascular lumens by balancing endothelial cytoskeletal dynamics and cell-matrix adhesion. [less ▲]

Detailed reference viewed: 61 (20 ULg)
Full Text
Peer Reviewed
See detailInteraction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program
Boxus, Mathieu ULg; Twizere, Jean-Claude ULg; Legros, Sébastien et al

in Blood (2012), 119

The Tax oncoprotein encoded by the Human T-cell leukemia virus type 1 (HTLV-1) plays a pivotal role in viral persistence and pathogenesis. HTLV-1 infected cells proliferate faster than normal lymphocytes ... [more ▼]

The Tax oncoprotein encoded by the Human T-cell leukemia virus type 1 (HTLV-1) plays a pivotal role in viral persistence and pathogenesis. HTLV-1 infected cells proliferate faster than normal lymphocytes, expand through mitotic division and accumulate genomic lesions. Here, we show that Tax associates with the minichromosome maintenance MCM2-7 helicase complex and localizes to origins of replication. Tax modulates the spatiotemporal program of origin activation and fires supplementary origins at the onset of S phase. Thereby, Tax increases the DNA replication rate, accelerates S phase progression but also generates a replicative stress characterized by the presence of genomic lesions. Mechanistically, Tax favors p300 recruitment and histone hyperacetylation at late replication domains advancing their replication timing in early S phase. [less ▲]

Detailed reference viewed: 28 (9 ULg)
Full Text
Peer Reviewed
See detailHost-pathogen interactome mapping for HTLV-1 and -2 retroviruses.
Simonis, Nicolas; Rual, Jean-Francois; Lemmens, Irma et al

in Retrovirology (2012), 9

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) and type 2 both target T lymphocytes, yet induce radically different phenotypic outcomes. HTLV-1 is a causative agent of Adult T-cell leukemia (ATL ... [more ▼]

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) and type 2 both target T lymphocytes, yet induce radically different phenotypic outcomes. HTLV-1 is a causative agent of Adult T-cell leukemia (ATL), whereas HTLV-2, highly similar to HTLV-1, causes no known overt disease. HTLV gene products are engaged in a dynamic struggle of activating and antagonistic interactions with host cells. Investigations focused on one or a few genes have identified several human factors interacting with HTLV viral proteins. Most of the available interaction data concern the highly investigated HTLV-1 Tax protein. Identifying shared and distinct host-pathogen protein interaction profiles for these two viruses would enlighten how they exploit distinctive or common strategies to subvert cellular pathways toward disease progression. RESULTS: We employ a scalable methodology for the systematic mapping and comparison of pathogen-host protein interactions that includes stringent yeast two-hybrid screening and systematic retest, as well as two independent validations through an additional protein interaction detection method and a functional transactivation assay. The final data set contained 166 interactions between 10 viral proteins and 122 human proteins. Among the 166 interactions identified, 87 and 79 involved HTLV-1 and HTLV-2 -encoded proteins, respectively. Targets for HTLV-1 and HTLV-2 proteins implicate a diverse set of cellular processes including the ubiquitin-proteasome system, the apoptosis, different cancer pathways and the Notch signaling pathway. CONCLUSIONS: This study constitutes a first pass, with homogeneous data, at comparative analysis of host targets for HTLV-1 and -2 retroviruses, complements currently existing data for formulation of systems biology models of retroviral induced diseases and presents new insights on biological pathways involved in retroviral infection. [less ▲]

Detailed reference viewed: 45 (9 ULg)
Full Text
Peer Reviewed
See detailDisruption of PDZ protein-protein interactions inhibits Tax transformation and HTLV-1 infection capacities.
Twizere, Jean-Claude ULg; DEWULF, Jean-François; Blibek, Karim ULg et al

Poster (2011, June 06)

Human T-cell leukemia virus type I (HTLV-1) encodes a Tax oncoprotein that is critical for both viral replication and cellular transformation. HTLV-1 Tax possesses a PDZ domain binding motif (PBM) at its ... [more ▼]

Human T-cell leukemia virus type I (HTLV-1) encodes a Tax oncoprotein that is critical for both viral replication and cellular transformation. HTLV-1 Tax possesses a PDZ domain binding motif (PBM) at its C-terminus that is essential for its transforming activity in a Rat-1 model and for IL-2. Tax has been shown to interact with several PDZ domain containing proteins including PSD-95, Beta1-syntrophin, the precursor of interleukin-16, the mammalian homolog of the Drosophila discs large tumor suppressor protein Dlg, PDLIM2, Lin7, hTid1, Tip1, hScrib and MAGI3. In the 15th International Conference on Human Retrovirology: HTLV and Related Retroviruses, we will present a specificity map for the Tax/PDZ domain interactions generated using the human ORFeome 5.1. and we will focus on some of the new Tax/PDZ interactions. [less ▲]

Detailed reference viewed: 48 (20 ULg)
Full Text
Peer Reviewed
See detailThe HTLV-1 Tax protein inhibits formation of stress granules by interacting with histone deacetylase 6.
Legros, S.; Boxus, Mathieu ULg; GATOT, Jean-Stéphane ULg et al

in Oncogene (2011)

Human T cell leukemia virus type-1 (HTLV-1) is the causative agent of a fatal adult T-cell leukemia. Through deregulation of multiple cellular signaling pathways the viral Tax protein has a pivotal role ... [more ▼]

Human T cell leukemia virus type-1 (HTLV-1) is the causative agent of a fatal adult T-cell leukemia. Through deregulation of multiple cellular signaling pathways the viral Tax protein has a pivotal role in T-cell transformation. In response to stressful stimuli, cells mount a cellular stress response to limit the damage that environmental forces inflict on DNA or proteins. During stress response, cells postpone the translation of most cellular mRNAs, which are gathered into cytoplasmic mRNA-silencing foci called stress granules (SGs) and allocate their available resources towards the production of dedicated stress-management proteins. Here we demonstrate that Tax controls the formation of SGs and interferes with the cellular stress response pathway. In agreement with previous reports, we observed that Tax relocates from the nucleus to the cytoplasm in response to environmental stress. We found that the presence of Tax in the cytoplasm of stressed cells prevents the formation of SGs and counteracts the shutoff of specific host proteins. Unexpectedly, nuclear localization of Tax promotes spontaneous aggregation of SGs, even in the absence of stress. Mutant analysis revealed that the SG inhibitory capacity of Tax is independent of its transcriptional abilities but relies on its interaction with histone deacetylase 6, a critical component of SGs. Importantly, the stress-protective effect of Tax was also observed in the context of HTLV-1 infected cells, which were shown to be less prone to form SGs and undergo apoptosis under arsenite exposure. These observations identify Tax as the first virally encoded inhibitory component of SGs and unravel a new strategy developed by HTLV-1 to deregulate normal cell processes. We postulate that inhibition of the stress response pathway by Tax would favor cell survival under stressful conditions and may have an important role in HTLV-1-induced cellular transformation.Oncogene advance online publication, 2 May 2011; doi:10.1038/onc.2011.120. [less ▲]

Detailed reference viewed: 73 (13 ULg)
Full Text
Peer Reviewed
See detailRecent insights into Protein Phosphatase 2A structure and regulation : The reason why PP2A is no longer considered as a lazy passive housekeeping enzyme
Martin, Maud ULg; Kettmann, Richard ULg; Dequiedt, Franck ULg

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (2010), 14(1), 243-252

Reversible protein phosphorylation is a major intracellular mechanism for controlling many important physiological activities. In the past, most of the attention was focused primarily on protein kinases ... [more ▼]

Reversible protein phosphorylation is a major intracellular mechanism for controlling many important physiological activities. In the past, most of the attention was focused primarily on protein kinases and on their regulation, mainly because phosphatases were then viewed as simple housekeeping enzymes. But advances in the understanding of phosphatases make now clear that protein phosphatases are dynamic and highly regulated enzymes and are as important as kinases in the regulation of cellular processes involving protein phosphorylation. Protein phosphatase 2A (PP2A) is a very abundant -it accounts for as much as 1% of total cellular protein-, ubiquitous and remarkably conserved enzyme. By dephosphorylating a plethora of cellular proteins, it is involved in the regulation of nearly all cellular activities. [less ▲]

Detailed reference viewed: 141 (3 ULg)
Full Text
Peer Reviewed
See detailEarlier onset of delta-retrovirus-induced leukemia after splenectomy.
Florins, ARNAUD-FRANCOIS ULg; Reichert, Michal; Asquith, Becca et al

in PLoS ONE (2009), 4(9), 6943

Infection by delta-retroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) is mostly asymptomatic. Indeed, only a minority (<5%) of delta-retrovirus infected hosts ... [more ▼]

Infection by delta-retroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) is mostly asymptomatic. Indeed, only a minority (<5%) of delta-retrovirus infected hosts will develop either lymphoproliferative or neurodegenerative diseases after long latency periods. In fact, the host immune response is believed to tightly control viral replication but this assumption has not been definitely proven in vivo. Here, we provide direct experimental evidence demonstrating that integrity of the spleen is required to control pathogenesis. In the BLV model, we show that asplenia decreases efficiency of the immune response and induces an imbalance in cell dynamics resulting in accelerated onset of leukemia. These observations enlighten a potential threat in splenectomized HTLV-1 carriers and justify a regular preventive evaluation. [less ▲]

Detailed reference viewed: 57 (19 ULg)
Full Text
Peer Reviewed
See detailProtein-protein interactions and gene expression regulation in HTLV-1 infected cells.
Legros, Sébastien ULg; Boxus, Mathieu ULg; Dewulf, Jean Francois et al

in Frontiers in Bioscience : A Journal and Virtual Library (2009), 14

Human T-cell leukemia virus type 1 (HTLV-1) propagates in CD4 or CD8 T cells and, after extended latency periods of 30-50 years, causes a rapidly fatal leukemia called adult T-cell leukemia/lymphoma (ATL ... [more ▼]

Human T-cell leukemia virus type 1 (HTLV-1) propagates in CD4 or CD8 T cells and, after extended latency periods of 30-50 years, causes a rapidly fatal leukemia called adult T-cell leukemia/lymphoma (ATL). Infection with HTLV-1 is also associated with a degenerative neuromuscular disease referred to as tropical spastic paraparesis or HTLV-1-associated myelopathy. HTLV genome, in addition to the structural proteins and retroviral enzymes, codes for a region at its 3' end originally designated pX. The products of this region (Tax, Rex, p12I, p13II, p30II and HBZ) play important roles in deregulation of cellular functions by either directly disrupting cellular factors or altering transcription of viral and cellular genes. Here, we will review current knowledge of protein-protein interactions that regulate transcriptional functions of proteins encoded by the pX region. [less ▲]

Detailed reference viewed: 82 (17 ULg)
Full Text
Peer Reviewed
See detailClass IIa histone deacetylases: conducting development and differentiation.
Martin, Maud ULg; Kettmann, Richard ULg; Dequiedt, Franck ULg

in International Journal of Developmental Biology (2009), 53(2-3), 291-301

The emergence of specialized cell types and their organisation into organs and tissues involve the temporal modulation of many genes that are essential for coordinating the correct timing of instructive ... [more ▼]

The emergence of specialized cell types and their organisation into organs and tissues involve the temporal modulation of many genes that are essential for coordinating the correct timing of instructive signals. These transcriptional changes are orchestrated with a precision that reminds that of a classical symphony. Extracellular signals are transmitted to key integrators, which then orchestrate activation or repression of specific genes. In the last decade, class IIa HDACs have emerged as crucial regulators in various developmental and differentiation processes. This review focuses on the latest studies that have provided new insights into the biological functions of class IIa HDACs and discusses important aspects of their regulation. Elucidating cellular and molecular mechanisms by which functions of class IIa HDACs are modulated could potentially lead to new therapeutic opportunities for various diseases. [less ▲]

Detailed reference viewed: 98 (4 ULg)
Full Text
Peer Reviewed
See detailProtein Phosphatase 2a Controls The Activity Of Histone Deacetylase 7 During T Cell Apoptosis And Angiogenesis
Martin, Maud ULg; Potente, M.; Janssens, V. et al

in Proceedings of the National Academy of Sciences of the United States of America (2008), 105(12), 4727-4732

Detailed reference viewed: 38 (14 ULg)
Full Text
Peer Reviewed
See detailEmphasis on cell turnover in two hosts infected by bovine leukemia virus: a rationale for host susceptibility to disease.
Florins, Arnaud-Francois ULg; Boxus, Mathieu ULg; Vandermeers, Fabian ULg et al

in Veterinary Immunology and Immunopathology (2008), 125(1-2), 1-7

Bovine leukemia virus (BLV) is a deltaretrovirus that infects and induces accumulation of B-lymphocytes in the peripheral blood and lymphoid tissues of cattle, leading to leukemia/lymphoma. BLV can also ... [more ▼]

Bovine leukemia virus (BLV) is a deltaretrovirus that infects and induces accumulation of B-lymphocytes in the peripheral blood and lymphoid tissues of cattle, leading to leukemia/lymphoma. BLV can also be experimentally transmitted to sheep, in which disease appears earlier and at higher frequencies. Abnormal accumulation of leukemic B-lymphocytes results from an alteration of different parameters that include cell proliferation and death as well as migration to lymphoid tissues. Interestingly, B lymphocyte turnover is increased in BLV-infected sheep but reduced in cattle, revealing a potential relationship between cell kinetics and disease progression. [less ▲]

Detailed reference viewed: 43 (20 ULg)
Full Text
Peer Reviewed
See detailImplication des modifications épigénétiques dans les cancers : développement de nouvelles approches thérapeutiques
Vandermeers, Fabian ULg; Kettmann, Richard ULg; Willems, Luc ULg

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (2008), 12(2),

Involvement of epigenetic modifications in cancers: development of new therapeutic approaches. Since cancer is the second cause of death after cardiovascular diseases in industrialized countries, it is ... [more ▼]

Involvement of epigenetic modifications in cancers: development of new therapeutic approaches. Since cancer is the second cause of death after cardiovascular diseases in industrialized countries, it is urgent to elaborate new therapeutic approaches. Besides DNA mutations of essential genes, expansion of a cancer cell is frequently associated with epigenetic modifications i.e. not directly coded by the DNA sequence. Amongst epigenetic modifications, histones acetylation and DNA methylation are known to play important roles. In this context, a very promising anticancer therapy would be to correct epigenetic errors using compounds modulating histone acetylation and DNA methylation alone or in combination with other chemotherapeutic agents. [less ▲]

Detailed reference viewed: 39 (11 ULg)
Full Text
Peer Reviewed
See detailThe HTLV-1 Tax interactome.
Boxus, Mathieu ULg; Twizere, Jean-Claude ULg; Legros, Sebastien et al

in Retrovirology (2008), 5

The Tax1 oncoprotein encoded by Human T-lymphotropic virus type I is a major determinant of viral persistence and pathogenesis. Tax1 affects a wide variety of cellular signalling pathways leading to ... [more ▼]

The Tax1 oncoprotein encoded by Human T-lymphotropic virus type I is a major determinant of viral persistence and pathogenesis. Tax1 affects a wide variety of cellular signalling pathways leading to transcriptional activation, proliferation and ultimately transformation. To carry out these functions, Tax1 interacts with and modulates activity of a number of cellular proteins. In this review, we summarize the present knowledge of the Tax1 interactome and propose a rationale for the broad range of cellular proteins identified so far. [less ▲]

Detailed reference viewed: 73 (31 ULg)
Full Text
Peer Reviewed
See detailLe virus de la leucemie bovine et l'homeostasie du compartiment lymphocytaire peripherique.
Florins, Arnaud-Francois ULg; Kettmann, Richard ULg; Willems, Luc ULg

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (2007), 11(1),

Detailed reference viewed: 21 (7 ULg)
Full Text
Peer Reviewed
See detailMechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human.
Gillet, Nicolas ULg; Florins, Arnaud-Francois ULg; Boxus, Mathieu ULg et al

in Retrovirology (2007), 4(1), 18

In 1871, the observation of yellowish nodules in the enlarged spleen of a cow was considered to be the first reported case of bovine leukemia. The etiological agent of this lymphoproliferative disease ... [more ▼]

In 1871, the observation of yellowish nodules in the enlarged spleen of a cow was considered to be the first reported case of bovine leukemia. The etiological agent of this lymphoproliferative disease, bovine leukemia virus (BLV), belongs to the deltaretrovirus genus which also includes the related human T-lymphotropic virus type 1 (HTLV-1). This review summarizes current knowledge of this viral system, which is important as a model for leukemogenesis. Recently, the BLV model has also cast light onto novel prospects for therapies of HTLV induced diseases, for which no satisfactory treatment exists so far. [less ▲]

Detailed reference viewed: 75 (14 ULg)
Full Text
Peer Reviewed
See detailEven attenuated bovine leukemia virus proviruses can be pathogenic in sheep.
Florins, Arnaud-Francois ULg; Gillet, Nicolas ULg; Boxus, Mathieu ULg et al

in Journal of virology (2007), 81(18), 10195-200

Based on a reverse genetics approach, we previously reported that bovine leukemia virus (BLV) mutants harboring deletions in the accessory R3 and G4 genes persist at very low proviral loads and are unable ... [more ▼]

Based on a reverse genetics approach, we previously reported that bovine leukemia virus (BLV) mutants harboring deletions in the accessory R3 and G4 genes persist at very low proviral loads and are unable to induce leukemia or lymphoma in sheep, indicating that these R3 and G4 gene sequences are required for pathogenesis. We now show that lymphoma can occur, albeit infrequently (1 case of 20) and after extended periods of latency (7 years). Direct sequencing and reinfection experiments demonstrated that lymphomagenesis was not due to the reversion of the mutant to the wild type. Similar observations with another type of attenuated mutant impaired in the transmembrane protein (TM) YXXL signaling motifs were made. We conclude that the R3 and G4 genes and the TM YXXL motifs are not strictly required for pathogenesis but that their integrity contributes to disease frequency and latency. [less ▲]

Detailed reference viewed: 83 (29 ULg)