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The human T-cell leukaemia virus type 1 (HTLV-1) is the first human retrovirus that has been discovered. It induces serious diseases including the adult T-cell leukaemia (ATL) and the HTLV-1-associated myopathy/tropical spastic paraparesis (HAM/TSP). Approximately 20 million people worldwide are infected with this oncogenic retrovirus, but only 5-10% will develop disease related to the infection. Tax, a trans-regulatory, activating nuclear oncoprotein, encoded by HLTV-1, has been identified as essential for cell replication and transformation. Preliminary data have shown that the helicase-like transcription factor (HLTF), a DNA damage tolerance regulator, is a restriction factor able to reduce HTLV-1 infectivity. These studies also demonstrated that HLTF interacts with Tax.
The objective of this undergraduate thesis is to evaluate the impact of Tax and HLTF on transcriptional activity directed by the HLTF promoter and the HTLV-1 long terminal repeat (LTR). Activation of the NF-κB pathway will also be evaluated in presence of wild-type and mutants of HLTF and Tax.
Data show that Tax mutants defective in NF-κB activation are expressed at lower levels compared to wild-type Tax. Luciferase reporter assays further show that Tax and HLTF mutants do not impact HLTF promoter activity. HLTF mutants do influence neither the transcription directed by the LTR nor the NF-κB pathway. Simultaneous induction of Tax and HLTF produces a synergistic effect on a NF-κB-AP-1-Luc reporter.
In summary, this work contributed to a better understanding of the mechanisms involved in the interactions between Tax and HLTF.

HTLV-1, HLTF, NF-κB, restriction factors, transcription factor --- Ingénierie, informatique & technologie > Ingénierie chimique

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Foamy viruses, currently referred to as spumaretroviruses, are the most ancient retroviruses as evidenced by traces of viral sequences dispersed in all vertebrate classes from fish to mammals. Additionally, infectious foamy viruses circulate in a variety of mammalian species including simian, bovine, equine, caprine, and feline. Foamy viruses have many unique features which led to the division of the retrovirus family into two subfamilies, the Orthoretrovirinae and Spumaretrovirinae. In vitro, foamy viruses have a broad host range and in vivo, human infections have been described due to cross-species transmission from infected nonhuman primates. Thus far, there are no reports of virus-induced disease in humans or in the natural host species. These unique properties of foamy viruses have led researchers to develop foamy viruses as gene therapy vectors to study virus–virus and virus–host interactions for identifying factors involved in virus replication, transmission, and immune regulation that could influence potential clinical outcomes in humans as well as for using endogenous foamy virus sequences in the analysis of host species evolution.

Medicine --- Neurosciences --- spumavirus --- feline illness --- proviral load --- neglected virus --- bovine foamy virus --- infectious clone --- particle release --- cell-free transmission --- foamy virus --- spumaretrovirus --- cross-species virus transmission --- zoonosis --- restriction factors --- immune responses --- FV vectors --- virus replication --- latent infection --- feline foamy virus --- epidemiology --- retrovirus --- Spumaretrovirus --- mountain lion --- Puma concolor --- ELISA --- protease --- reverse transcriptase --- RNase H --- reverse transcription --- antiviral drugs --- resistance --- simian foamy virus --- gibbon --- lesser apes --- co-evolution --- complete viral genome --- equine foamy virus --- isolation --- Japan --- sero-epidemiology --- reptile foamy virus --- endogenous foamy virus --- endogenous retrovirus --- ancient retroviruses --- co-speciation --- foamy virus-host interactions --- viral tropism --- infection --- kidney --- cats --- chronic kidney disease --- chronic renal disease --- integrase --- integration --- co-infections --- NHP --- pathogenesis --- zoonoses --- viral prevalence --- Neotropical primates --- free-living primates --- Brazil --- new world primates --- simian retrovirus --- BFV --- spuma virus --- model system --- animal model --- animal experiment --- miRNA function --- gene expression --- antiviral host restriction --- gene therapy --- in-vivo gene therapy --- hematopoietic stem and progenitor cells --- foamy virus vector --- pre-clinical canine model --- SCID-X1 --- innate sensing --- cGAS --- STING --- foamy viruses --- wild ruminants --- European bison --- red deer --- roe deer --- fallow deer --- seroreactivity --- inter-species transmission --- HSC --- gene marking --- FV gene transfer to HSCs --- gene therapy alternatives --- serotype --- high-throughput sequencing --- replication kinetics --- cytopathic effect --- reverse transcriptase activity --- miRNA expression --- virus-host-interaction --- miRNA target gene identification --- innate immunity --- ANKRD17 --- Bif1 (SH3GLB1) --- replication in vitro --- spumavirus --- feline illness --- proviral load --- neglected virus --- bovine foamy virus --- infectious clone --- particle release --- cell-free transmission --- foamy virus --- spumaretrovirus --- cross-species virus transmission --- zoonosis --- restriction factors --- immune responses --- FV vectors --- virus replication --- latent infection --- feline foamy virus --- epidemiology --- retrovirus --- Spumaretrovirus --- mountain lion --- Puma concolor --- ELISA --- protease --- reverse transcriptase --- RNase H --- reverse transcription --- antiviral drugs --- resistance --- simian foamy virus --- gibbon --- lesser apes --- co-evolution --- complete viral genome --- equine foamy virus --- isolation --- Japan --- sero-epidemiology --- reptile foamy virus --- endogenous foamy virus --- endogenous retrovirus --- ancient retroviruses --- co-speciation --- foamy virus-host interactions --- viral tropism --- infection --- kidney --- cats --- chronic kidney disease --- chronic renal disease --- integrase --- integration --- co-infections --- NHP --- pathogenesis --- zoonoses --- viral prevalence --- Neotropical primates --- free-living primates --- Brazil --- new world primates --- simian retrovirus --- BFV --- spuma virus --- model system --- animal model --- animal experiment --- miRNA function --- gene expression --- antiviral host restriction --- gene therapy --- in-vivo gene therapy --- hematopoietic stem and progenitor cells --- foamy virus vector --- pre-clinical canine model --- SCID-X1 --- innate sensing --- cGAS --- STING --- foamy viruses --- wild ruminants --- European bison --- red deer --- roe deer --- fallow deer --- seroreactivity --- inter-species transmission --- HSC --- gene marking --- FV gene transfer to HSCs --- gene therapy alternatives --- serotype --- high-throughput sequencing --- replication kinetics --- cytopathic effect --- reverse transcriptase activity --- miRNA expression --- virus-host-interaction --- miRNA target gene identification --- innate immunity --- ANKRD17 --- Bif1 (SH3GLB1) --- replication in vitro

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• EndNote
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Foamy viruses, currently referred to as spumaretroviruses, are the most ancient retroviruses as evidenced by traces of viral sequences dispersed in all vertebrate classes from fish to mammals. Additionally, infectious foamy viruses circulate in a variety of mammalian species including simian, bovine, equine, caprine, and feline. Foamy viruses have many unique features which led to the division of the retrovirus family into two subfamilies, the Orthoretrovirinae and Spumaretrovirinae. In vitro, foamy viruses have a broad host range and in vivo, human infections have been described due to cross-species transmission from infected nonhuman primates. Thus far, there are no reports of virus-induced disease in humans or in the natural host species. These unique properties of foamy viruses have led researchers to develop foamy viruses as gene therapy vectors to study virus–virus and virus–host interactions for identifying factors involved in virus replication, transmission, and immune regulation that could influence potential clinical outcomes in humans as well as for using endogenous foamy virus sequences in the analysis of host species evolution.

spumavirus --- feline illness --- proviral load --- neglected virus --- bovine foamy virus --- infectious clone --- particle release --- cell-free transmission --- foamy virus --- spumaretrovirus --- cross-species virus transmission --- zoonosis --- restriction factors --- immune responses --- FV vectors --- virus replication --- latent infection --- feline foamy virus --- epidemiology --- retrovirus --- Spumaretrovirus --- mountain lion --- Puma concolor --- ELISA --- protease --- reverse transcriptase --- RNase H --- reverse transcription --- antiviral drugs --- resistance --- simian foamy virus --- gibbon --- lesser apes --- co-evolution --- complete viral genome --- equine foamy virus --- isolation --- Japan --- sero-epidemiology --- reptile foamy virus --- endogenous foamy virus --- endogenous retrovirus --- ancient retroviruses --- co-speciation --- foamy virus-host interactions --- viral tropism --- infection --- kidney --- cats --- chronic kidney disease --- chronic renal disease --- integrase --- integration --- co-infections --- NHP --- pathogenesis --- zoonoses --- viral prevalence --- Neotropical primates --- free-living primates --- Brazil --- new world primates --- simian retrovirus --- BFV --- spuma virus --- model system --- animal model --- animal experiment --- miRNA function --- gene expression --- antiviral host restriction --- gene therapy --- in-vivo gene therapy --- hematopoietic stem and progenitor cells --- foamy virus vector --- pre-clinical canine model --- SCID-X1 --- innate sensing --- cGAS --- STING --- foamy viruses --- wild ruminants --- European bison --- red deer --- roe deer --- fallow deer --- seroreactivity --- inter-species transmission --- HSC --- gene marking --- FV gene transfer to HSCs --- gene therapy alternatives --- serotype --- high-throughput sequencing --- replication kinetics --- cytopathic effect --- reverse transcriptase activity --- miRNA expression --- virus-host-interaction --- miRNA target gene identification --- innate immunity --- ANKRD17 --- Bif1 (SH3GLB1) --- replication in vitro