Дисертації з теми "Protein-HIV Virus"
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Douglas, Chanel Catherine. "A study into the protein/protein interactions involved in HIV-1 capsid assembly." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2008r/douglas.pdf.
Повний текст джерелаSeckler, James Malcolm. "The Structural Dynamics of Human Immunodeficiency Virus Type I Reverse Transcriptase." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1298562809.
Повний текст джерелаApcher, Géraud-Sébastien. "HIV-1 Tat protein and proteasomal Subunit Interactions." Clermont-Ferrand 2, 2003. http://www.theses.fr/2003CLF21470.
Повний текст джерелаAbdurahman, Samir. "Studies on HIV-1 core assembly /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-363-4/.
Повний текст джерелаLeung, Sze-ki, and 梁詩琪. "Mechanism of human immunodeficiency virus induced immunedysregulation: TAT & IL-18 interaction." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B34605472.
Повний текст джерелаAntonucci, Jenna Marie. "Mechanisms of HIV-1 Restriction by the Host Protein SAMHD1." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1524006072232491.
Повний текст джерелаLeung, Sze-ki. "Mechanism of human immunodeficiency virus induced immune dysregulation TAT & IL-18 interaction /." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B34605472.
Повний текст джерелаPostupalenko, Viktoriia. "Ratiometric fluorophores for peptides and oligonucleotides labeling : application to the HIV-1 nucleocapsid protein." Strasbourg, 2011. https://publication-theses.unistra.fr/public/theses_doctorat/2011/POSTUPALENKO_Viktoriia_2011_ED414.pdf.
Повний текст джерелаThis work focuses on the development of a methodology for sensing interactions of proteins with oligonucleotides (ODNs) and membranes based on fluorescent probes from the 3-hydroxychromone (3HC) family. Due to an excited state intramolecular proton transfer, these dyes exhibit two highly resolved emission bands, differently sensitive to the environment, thus allowing to sense interactions through their intensity ratio changes. An amino acid analogue based on 3HC was synthesized and inserted at selected positions of the HIV-1nucleocapsid protein (NC), to further characterize the peptide-ODNs interaction and provide site-specific information on the environmental changes induced by the interaction close to the labeling site. As an alternative, fluorescent nucleosides were synthesized and applied to different positions of ODNs. To study the peptide-membrane interactions, 3HC probe sensitive to polarity changes in apolar solvents was coupled to the N-terminus of melittin, magainin and poly-L-lysine peptides, known to interact with lipid membranes. The observed intensity ratio of the probe correlates well with the insertion depth of the N-terminal region of the peptides. Finally, we applied this dye for the detection of possible interactions of NC with membranes. We have shown that NC binds with high affinity to membranes containing negatively charged lipids. This interaction is mainly driven by electrostatic forces and locates NC at the level of lipid heads. Moreover, NC destabilizes the membrane in a concentration-dependent manner. As free NC, NC-DNA complexes can also bind to membranes, suggesting an involvement of NC in the nuclear import of the pre-integration complex
Zheng, Yingfeng. "Functional analysis on the interactions of the human immunodeficiency virus type 1 integrase with its cofactors that regulate viral replication." BioMed Central Ltd, 2008. http://hdl.handle.net/1993/16248.
Повний текст джерелаZhang, Wei Hong. "Studies on structure and function of human immunodeficiency virus type one (HIV-1) Gag protein." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.320175.
Повний текст джерелаDjekic, Uros V. "Coupling selection of the HIV-1 tRNA primer used for reverse transcription with viral translation and encapsidation." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2008r/djekic.pdf.
Повний текст джерелаDupont, Stefan A. "The Functional Roles of the Human Immunodeficiency Virus Type-1 Matrix Protein during Viral Life Cycle: A Dissertation." eScholarship@UMMS, 2000. http://escholarship.umassmed.edu/gsbs_diss/191.
Повний текст джерелаNowak, Piotr. "Aspects of immune activation in HIV-1 infection /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-190-6/.
Повний текст джерелаJohnson, Jacklyn. "Properties of HIV-1 env and human seminal fluid that determine virus inhibition by antibodies and microbicides." Diss., University of Iowa, 2019. https://ir.uiowa.edu/etd/6966.
Повний текст джерелаChaudhuri, Rittik. "The mechanism of HIV-1 Nef-mediated downregulation of CD4." Thesis, University of Cambridge, 2010. https://www.repository.cam.ac.uk/handle/1810/224775.
Повний текст джерелаKim, Adonia Lee. "The Role of Adaptor Protein Complex-3 Delta-Mediated HIV-1 Gag Trafficking in HIV-1 Replication: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/612.
Повний текст джерелаWarncke, Malte L. [Verfasser], and Hans-Willi [Akademischer Betreuer] Mittrücker. "Generation of bispecific antibodies against the human immunodeficiency virus (HIV) envelope protein / Malte L. Warncke. Betreuer: Hans-Willi Mittrücker." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2013. http://d-nb.info/1037822560/34.
Повний текст джерелаRomani, Bizhan. "Mutagenesis and functional studies of the HIV-1 vpr gene and Vpr protein obtained from South African virus strains." Thesis, Stellenbosch : University of Stellenbosch, 2010. http://hdl.handle.net/10019.1/6702.
Повний текст джерелаENGLISH ABSTRACT: Background: Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is an accessory protein that interacts with a number of host cellular and other viral proteins. Vpr exerts several functions such as induction of apoptosis, induction of cell cycle G2 arrest, modulation of gene expression, and suppression of immune activation. The functionality of subtype C Vpr, especially South African strains, has not been studied. The aim of this study was to describe the diversity of South African HIV-1 subtype C vpr genes and to investigate selected functions of these Vpr proteins. Methodology: The HIV-1 vpr region of 58 strains was amplified, sequenced, and subtyped using phylogenetic analysis. Fragments containing natural mutations were cloned in mammalian expression vectors. A consensus subtype C vpr gene was constructed and site-directed mutagenesis was used to induce mutations in postions in which no natural mutations have been described. The functionality of all constructs was compared with the wild-type subtype B Vpr, by transfecting human 293T cell line to investigate subcellular localization, induction of apoptosis and cell cycle G2 arrest. The modulation of genes expressed in the induction of apoptosis using TaqMan Low density arrays (TLDA) was also investigated. Results: Phylogenetic analysis characterized 54 strains as HIV-1 subtype C and 4 strains as HIV-1 subtype B. The overall amino acid sequence of Vpr was conserved including motifs FPRPWL and TYGDTW, but the C-terminal was more variable. The following mutations were constructed using site-directed mutagenesis: P14I, W18C, Y47N, Q65H and Q88S. Subtype B and all natural mutants of subtype C Vpr localized to the nucleus but the W18C mutation disturbed the nuclear localization of Vpr. The cell cycle G2 arrest activity of all the mutants, as well as consensus-C, was lower than that of subtype B Vpr. All the natural mutants of subtype C Vpr induced cell cycle G2 arrest in 54.0-66.3% of the cells, while subtype B Vpr induced cell cycle G2 arrest in 71.5% of the cells. Subtype B and the natural mutant Vpr proteins induced apoptosis in a similar manner, ranging from 95.3-98.6% of transfected cells. However, an artificially designed Vpr protein containing the consensus sequences of subtype C Vpr indicated a reduced ability to induce apoptosis. While consensus-C Vpr induced apoptosis in only 82.0% of the transfected cells, the artificial mutants of Vpr induced apoptosis in 88.4 to 96.2% of the cells. The induction of apoptosis associated gene expression was similar for all constructs, indicated that apoptosis was efficiently induced through the intrinsic pathway by the mutants. Conclusion: This study indicated that both HIV-1 subtype B and C Vpr display a similar ability for nuclear localization and apoptosis induction. The induction of cell cycle G2 arrest by HIV-1 subtype B Vpr may be more robust than many subtype C Vpr proteins. The natural mutations studied in the isolates did not disturb the functions of subtype C Vpr and in some cases even potentiated the protein to induce apoptosis. Naturally occurring mutations in HIV-1 Vpr cannot be regarded as defective, since enhanced functionality would be more indicative of an adaptive role. The increased potency of the mutated Vpr proteins suggests that Vpr may increase the pathogenicity of HIV-1 by adapting apoptotic enhancing mutations.
AFRIKAANSE OPSOMMING: Agtergrond: Die virus protein R (Vpr) van Menslike Immuungebrek Virus tipe 1 (MIV-1) is ‘n bykomstige protein wat met ‘n aantal sellulêre proteine van die gasheer en ander virus proteine in wisselwerking tree. Vpr het 'n invloed op verskeie funksies onder andere die induksie van apoptose, die induksie van selsiklus G2 staking, modulering van geen uitdrukking en onderdrukking van immuun aktivering. Die funksionaliteit van subtipe C Vpr, en veral die van Suid-Afrikaanse stamme, is nie beskryf nie. Die doelwit van die studie was om die diversiteit van Suid Afrikaanse MIV-1 subtipe C vpr gene te beskryf en ook om selektiewe funksies van die Vpr proteine te ondersoek Metodiek: Die MIV-1 vpr streek van 58 stamme is vermeerder, die DNA volgordes is bepaal en die stamme is gesubtipeer deur filogenetiese analise. Fragmente met natuurlike mutasies is in ekspressie vektore gekloon. ‘n Konsensus subtipe C Vpr geen is ontwerp en mutasies in posisies waar geen natuurlike mutasies beskryf is nie, is ontwerp deur mutagenese. Die funksionaliteit van die konstrukte is met die wilde tipe subtype B vergelyk deur 293T sellyn te transfekteer en te ondersoek vir subsellulêre lokalisering, induksie van apoptose, en G2 selsiklus stilstand. Die modulering van geen uitdrukking in die induksie van apoptose is deur TLDA ondersoek. Resultate: Filogenetiese analise het 54 stamme as HIV-1 subtipe C geklassifiseer en 4 stamme as subtype B. Die Vpr aminosuur volgordes was konstant insluitend die FPRPWL en TYGDTW motiewe, maar die C-terminaal was meer variëerbaar. Deur mutagenese is die volgende mutasies ontwerp: P14I, W18C, Y47N, Q65H and Q88S. Subtipe B en al die natuurlike mutante van subtipe C het in die selkern gelokaliseer, maar die W18C mutasie het die lokalisasie versteur. Die G2 selsiklus stilstand van alle mutante en konsensus C was laer as die van subtype B. Al die natuurlike subtipe C mutante het G2 selsiklus tot stilstand gebring in 54.0-66.3% van die selle, terwyl subtype B selsiklus tot stilstand gebring het in 71.5% van die selle. Subtipe B en die natuurlike Vpr mutante het apoptose op ‘n soortgelyke wyse geinduseer, wat wissel tussen 95.3-98.6% van getransfekteerde selle. Die protein met die kunsmatig ontwerpte konsensus C volgorde het egter ‘n verlaagde vermoë gehad om apoptose te induseer. Die konsensus subtipe C het apoptose in 82.0% van getransfekteerde selle geinduseer en die kunsmatige mutante in 88.4 – 96.2% van die selle. Die induksie van die apoptose verwante geen ekspressie deur die mutante was soortgelyk as die van konsensus C en subtipe B Vpr wat ’n aangeduiding is dat apoptose effektief veroorsaak is deur die intrinsieke roete. Gevolgtrekking: Hierdie studie het aangetoon dat kern lokalisering en apoptose op ‘n soortgelyke wyse by beide MIV-1 subtipe B en C Vpr plaasvind. Die induksie van selsiklus G2 stilstand deur MIV-1 subtipe B Vpr is egter meer robuust as baie van die subtipe C Vpr proteïene. Natuurlike mutasies in MIV-1 Vpr kan nie as gebrekkig beskou word nie, aangesien beter funksionaliteit 'n aanduiding is vandie aanpasbare rol. Die verhoogde krag van die gemuteerde Vpr proteïen dui daarop dat Vpr die patogenisiteit van MIV-1 kan verbeter deur die aanpassing van mutasies.
Vaine, Michael. "Antibody Responses Elicited by DNA Prime-Protein Boost HIV Vaccines: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/462.
Повний текст джерелаShandilya, Shivender. "Structural Studies of the Anti-HIV Human Protein APOBEC3G Catalytic Domain: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/562.
Повний текст джерелаCosta, Matthew R. "FC Receptor-Mediated Activities of Env-Specific Monoclonal Antibodies Generated from Human Volunteers Receiving a DNA Prime-Protein Boost HIV Vaccine: A Dissertation." eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/866.
Повний текст джерелаCosta, Matthew R. "FC Receptor-Mediated Activities of Env-Specific Monoclonal Antibodies Generated from Human Volunteers Receiving a DNA Prime-Protein Boost HIV Vaccine: A Dissertation." eScholarship@UMMS, 2010. http://escholarship.umassmed.edu/gsbs_diss/866.
Повний текст джерелаSercovich, Mark J. "Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr)-mediated cell cycle arrest : an analysis of current mechanistic models /." Download the thesis in PDF, 2006. http://www.lrc.usuhs.mil/dissertations/pdf/sercovich2006.pdf.
Повний текст джерелаKulkarni, Amod Prakash. "Delivery of Vaccinia Virus Complement Control Protein (VCP) and Curcumin to the rodents' brain : implications in Alzheimer's disease and HIV dementia." Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/3286.
Повний текст джерелаSánchez-Velar, Nuria. "The Human Rev Interacting Protein (hRIP) is Required for Rev Function and HIV-1 Replication: a Dissertation." eScholarship@UMMS, 2005. http://escholarship.umassmed.edu/gsbs_diss/312.
Повний текст джерелаChitongo, Rumbidzai. "Investigating the structural effect of Raltegravir resistance associated mutations on the South African HIV-1 Integrase subtype C protein structure." University of the Western Cape, 2020. http://hdl.handle.net/11394/8075.
Повний текст джерелаBackground and Aims Human Immunodeficiency Virus (HIV) type 1 group M subtype C (HIV-1C) accounts for nearly half of global HIV-1 infections, with South Africa (SA) being one of the countries with the highest infection burden. In recent years, SA has made great strides in tackling its HIV epidemic, resulting in the country being recognized globally as the one sub-Saharan country with the largest combination antiretroviral therapy (cART) programme. Regardless of the potency of cART, the efficacy of the treatment is limited and hampered by the emergence of drug resistance. The majority of research on HIV-1 infections, effect of antiretroviral (ARV) drugs and understanding resistance to ARV drugs has been extensively conducted, but mainly on HIV-1 subtype B (HIV-1B), with less information known about HIV-1C. HIV-1’s viral Integrase (IN) enzyme has become a viable target for highly specific cART, due to its importance in the infection and replication cycle of the virus. The lack of a complete HIV-1C IN protein structure has negatively impacted the progress on structural studies of nucleoprotein reaction intermediates. The mechanism of HIV-1 viral DNA’s integration has been studied extensively at biochemical and cellular levels, but not at a molecular level. This study aims to use in silico methods that involve molecular modeling and molecular dynamic (MD) simulations to prioritize mutations that could affect HIV-1C IN binding to DNA and the IN strand-transfer inhibitor (INSTI) dolutegravir (DTG). The purpose is to help tailor more effective personalized treatment options for patients living with HIV in SA. This study will in part use patient derived sequence data to identify mutations and model them into the protein structure to understand their impact on the HIV-1C IN protein structure folding and dynamics. Methods Our sample cohort consisted of 11 sample sequences derived from SA HIV-1 treatmentexperienced patients who were being treated with the INSTI raltegravir (RAL). The sequences were submitted to the Stanford HIV resistance database (HIVdb) to screen for any new/novel variants resulting from possible RAL failure. Some of these new variants were analyzed to analyse their effect, if any, on the binding of DTG to the HIV-1C IN protein. Additionally, an HIV-1C IN consensus sequence constructed from SA’s HIV-1 infected population was used to model a complete three-dimensional wild type (WT) HIV-1C IN homology model. All samples were sequenced by our collaborators at the Division of Medical Virology, Stellenbosch University together with the National Health Laboratory Services (NHLS), SA. The HIV-1CZA WT-IN protein enzyme was predicted using SWISS-MODEL, and the quality of the resulting model validated. Various analyses were conducted in order to study and assess the effect of the selected new variants on the protein structure and binding of DTG to the IN protein. The mutation Cutoff Scanning Matrix (mCSM) program was used to predict protein stability after mutation, while PyMol helped to study any changes in polar contact activity before and after mutation. PyMol was also used to generate four mutant HIV-1C IN complex structures and these structures together with the WT IN were subjected to production MD simulations for 150 nanoseconds (ns). Trajectory analyses of the MD simulations were also conducted and reported. Results A total of 21 new variants were detected in our sample cohort, from which only six were chosen for further analyses within the study. A homology model of HIV-1C IN was successfully constructed and validated. The structural quality assessment indicated high reliability of the HIV-1C IN tetrameric structure, with more than 90.0% confidence in modelled regions. Of the six selected variants, only one (S119P) was calculated to be slightly stabilizing to the protein structure, with the other five found to be destabilizing to the IN protein structure. Variant S119P showed a loss in polar contacts that could destabilize the protein structure, while variant Y143R, resulted in the gain of polar contacts which could reduce flexibility of the 140’s region affecting drug binding. Similarly, mutant systems P3 (S119P, Y143R) and P4 (V150A, M154I) showed reduced hydrogen bond formation and the weakest non-bonded pairwise interaction energy. These two systems, P3 and P4, also showed significantly reduced to none polar contacts between DTG, magnesium (MG) ions and the IN protein, compared to the WT IN and P2 mutant IN systems. Interestingly, the WT structure and systems P1 (I113V) and P2 (L63I, V75M, Y143R) showed the highest non-bonded interaction energy, compared to systems P3 and P4. This was further supported by the polar interaction analyses of simulation clusters from the WT IN and mutant IN system P2 (L63I, V75M, Y143R), which were the only protein structures that formed polar contacts with DTG, MG ions and DDE motif residues, while P1 only made contacts with DNA and IN residues. Conclusion Findings from this study leads to a conclusion that double mutants (S119P, Y143R) and (V150A, M154I) may result in a reduction in the efficacy of DTG, especially when in combination. Furthermore, variants identified in systems P1 and P2 may still allow for effective DTG binding to IN and outcompete viral DNA for host DNA to prevent strand transfer. To the best of our knowledge, this is the first study that uses the consensus WT HIV1C IN sequence to build an accurate 3D homology model to understand the effect of less frequently detected/reported variants on DTG binding in a South African context. https://etd.
Oyeyemi, Oyebode. "Modelling HIV-1 interaction with the host system." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/modelling-hiv1-interaction-with-the-host-system(41095e34-78dd-4b75-bd25-9695a4cc768f).html.
Повний текст джерелаLê-Bury, Gabrielle. "Infection des macrophages par le VIH-1 : facteurs moléculaires impliqués dans la production virale et dans le développement de bactéries opportunistes The HIV-1 protein Vpr impairs phagosome maturation by controlling microtubule-dependent trafficking Pronounced stealth phenotype and differential pyroptosis induction by invasive Salmonella Typhimurium revealed by coinfection of human macrophages with HIV Role of Solute Carriers in efficient HIV-1 production by human macrophages." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB094.
Повний текст джерелаHuman Immunodeficiency Virus type 1 (HIV-1) infects macrophages. In contrast to CD4+ T cells, macrophages are resistant to the cytotoxic effects of the virus and represent a reservoir for the pathogen. In these cells, the new virions are produced and stored in a specific intracellular compartment called Virus-Containing Compartment (VCC). This non-acidic compartment, transiently connected to the plasma membrane, remains poorly characterized. In addition, HIV-1 induces an alteration of macrophage function, allowing the development of opportunistic bacteria, such as specific strains of Salmonella Typhimurium. In particular, we studied invasive non-typhoidal Salmonella Typhimurium (iNTS) strains that developed in HIV-positive patients. The aims of my thesis have been to identify the molecular factors involved in the production of HIV-1 in primary human macrophages and to study the development of the invasive strains of Salmonella Typhimurium. First, I participed in studying the effects of HIV-1 infection on macrophage function. Their main role is phagocytosis, which is a defense mechanism enabling internalization and degradation of pathogens. It has previously been shown in the host laboratory that in HIV-1 infected macrophages, the internalization step is partially inhibited by the virulence factor Nef. In this work, we have shown that the infection of these cells by HIV-1 also inhibits the maturation of phagosomes, in this case, via the viral protein Vpr. Further, we have demonstrated that HIV-1 leads to a pre-activation state of the macrophage, while preventing the cell from responding to subsequent stimuli, such as bacterial superinfection. Secondly, I studied the coinfections between HIV-1 and an invasive strain of Salmonella Typhimurium that was compared to reference strains. This work demonstrated that bacteria do not hijack the viral compartment for their survival in co-infected macrophages. Additionally, the invasive strain of Salmonella Typhimurium was observed to induce less cell death by pyroptosis than a reference strain. The signaling pathways upstream of this cell death were determined to be associated with an inflammatory mechanism. Hence, it was demonstrated that the invasive strain of Salmonella hijacks the mechanism of pyroptosis to survive in macrophages. This may explain the dissemination observed in patients. Finally, a study of new cellular factors involved in viral production in macrophages was conducted. Following a transcriptomic analysis of human primary macrophages infected, or not, with HIV-1, we identified a large number of membrane transporters called SLC (Solute Carrier) whose expression was modulated by the infection. After selecting some of the candidates for further study, I have demonstrated that some of these SLCs are important for viral production in macrophages. In conclusion, this work contributes to defining how HIV-1 infects macrophages and disturbs their activation and clearance functions, and how opportunistic pathogenic bacteria develop
Roes, Claas Verfasser], Dieter [Akademischer Betreuer] [Willbold, and Bernd [Akademischer Betreuer] König. "Structural investigation of the interaction of the human BST2 with the HIV-1 Virus protein U / Claas Roes. Gutachter: Dieter Willbold ; Bernd König." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2015. http://d-nb.info/1069985880/34.
Повний текст джерелаLee, Se Il. "Statistical thermodynamics of virus assembly." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/33900.
Повний текст джерелаYandrapalli, Naresh. "Role of HIV-1 Gag protein multimerization in the generation of nanodomains in lipid membranes." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT097/document.
Повний текст джерелаGag polyprotein of HIV-1 is made of four main domains Matrix (MA), Capsid (CA), Nucleocapsid (NC), and P6 and is the prime orchestrator of virus assembly that occurs during the late phase of replication. It is well known that Gag interacts with host cell lipids and self-assemble along the inner-leaflet of the plasma membrane in order to generate virus like particles (VLPs). Budding of these VLPs out of the living cell is described to be ESCRT dependent. Structural, functional and simulation based studies has shown that Gag membrane binding is mediated by a bipartite interaction. One specific electrostatic interaction, between the highly basic region (HBR) of its MA domain and the host cell acidic lipid phosphatidyl inositol bisphophate (PI(4,5)P2), plus a hydrophobic interaction through Gag’s myristate insertion in the plasma membrane. It is still an opened question whether Gag would specifically recognize pre-existing lipid domains such as rafts to optimize its multimerization or, on the contrary, would reorganize lipids during its multimerization. During my Ph.D. I explored the second hypothesis using purified myr(-) Gag protein and model membranes containing fluorescently labelled PI(4,5)P2.Bonding experiments have shown strong affinities of these purified proteins towards PI(4,5)P2 containing lipid bilayers. Using PI(4,5)P2 fluorescence self-quenching properties, I found that multimerization Gag generates PI(4,5)P2/Cholesterol enriched nanoclusters. On the opposite, sphingomyelin was excluded from these nanoclusters. In addition to this, using a fluorescently labelled myr(-) Gag, I have observed its preferable partitioning into lipid disordered (Ld) phases of giant unilamellar vesicles (GUVs). Further, possibility of whether HIV-1 Gag alone, as a minimal system, can induce the formation of vesicles on PI(4,5)P2/PS containing supported lipid bilayers (SLBs) & GUVs was tested. Using quartz crystal microbalance (QCM-D) and fluorescence microscopy techniques, I monitored the self-assembly of HIV-1 Gag with time and found that Gag was sufficient to generate membrane curvature and vesicle release. Moreover, using mutants of this protein, I found that having MA and CA domain is enough for Gag to produce vesicle like structures. Taken together, these results suggest that binding and multimerization of Gag protein does not occur in pre-existing lipid domains (such as “rafts”) but this multimerization is more likely to induce PI(4,5)P2/Cholesterol nanoclusters. This nanophase separation could locally play a role in the membrane curvature needed for the budding of the virus
Hinton, Michael. "Cellular Mechanisms by which Alcohol Promotes HIV Protease Inhibitor-induced Hepatotoxicity." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/6089.
Повний текст джерелаChen, Yuxin. "Characterization of Envelope-Specific Antibody Response Elicited by HIV-1 Vaccines: A Dissertation." eScholarship@UMMS, 2015. https://escholarship.umassmed.edu/gsbs_diss/760.
Повний текст джерелаChen, Yuxin. "Characterization of Envelope-Specific Antibody Response Elicited by HIV-1 Vaccines: A Dissertation." eScholarship@UMMS, 2001. http://escholarship.umassmed.edu/gsbs_diss/760.
Повний текст джерелаChougui, Ghina. "Antagonism of HUSH restriction by lentiviral Vpx and Vpr proteins HIV-2/SIV viral protein X counteracts HUSH repressor complex." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB080.
Повний текст джерелаHIV-1 and 2 are both responsible for AIDS, though similar, these two retroviruses harbour different sets of auxiliary proteins. Through the inactivation of cellular antiviral factors, these auxiliary proteins allow the establishment of a favourable environment for viral replication. Vpx, an HIV-2 only auxiliary protein, is known for its ability to increase viral infection, which was long linked to its sole capacity to counteract SAMHD1, a restriction factor active at the reverse transcription step. However, several lines of evidence suggested a SAMHD1-independent advantage of Vpx. We therefore investigated the possibility of an additional Vpx target and through a proteomic screen, we identified the HUman Silencing Hub (HUSH) complex. HUSH complex, including: TASOR, MPP8 and Periphelin, was reported to epigenetically silence integrated transgenes and recently Line-1 transposable elements. Here, we show that Vpx binds the HUSH complex and induces its proteasomal degradation through the hijacking of the DCAF-1 ubiquitin ligase adaptor, independently from SAMHD1-antagonism. As a consequence, Vpx is able to reactivate HIV latent proviruses, unlike Vpx mutants unable to induce HUSH degradation. Although antagonism of human HUSH complex is not conserved among all lentiviral lineages including HIV-1, it is a feature of Vpr from SIVs of African green monkeys and from the divergent SIV of l'Hoest's monkey, arguing in favor of an ancient lentiviral species-specific vpx/vpr gene function. Altogether, our results highlight an unexpected post-integration activity of Vpx and suggest HUSH complex as a restriction factor. They also support the idea of epigenetic control as an intrinsic immunity barrier maintaining the integrity of the cellular genome
Hérate, Cécile. "Contribution de la forme nucléaire de l'uracile DNA glycosylase aux étapes précoces du cycle de réplication du virus de l'immunodéficience humaine de type 1." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015PA05T017/document.
Повний текст джерелаThe HIV-1 auxiliary protein Vpr is expressed during the late steps of the viral replication. However, Vpr is incorporated into HIV-1 viral particles and plays a key role during the initial steps of the viral replication cycle. This 96 amino acids protein is involved in viral genome reverse transcription as well as in viral DNA translocation into the nucleus of the host cell. In parallel, Vpr provokes cell cycle arrest and apoptosis of infected T cells. Previously, it has been well established that Vpr participates in the control of the fidelity of the reverse transcription through the recruitment of the Uracil DNA Glycosylase 2 (UNG2) into the viral particles. UNG2 is an enzyme involved in different DNA repair pathway. However some studies have challenged the positive impact of UNG2 encapsidation for HIV-1 replication. Here, our studies confirm the important role of UNG2 for the control of the mutation rate in the newly synthesized viral DNA by a mechanism independent of its enzymatic activity but dependent to determinants located in the N-terminal domain that is involved in the recruitment of the p32 subunit of the RPA (Replication Protein A) complex (RPA32). First we showed that viruses produced in UNG2 or RPA32 depleted cells present a defect of infectivity and that the reverse transcription step is impaired during the course of infection of these viruses. Then we reported that the Vpr protein is able to form a trimolecular complex with UNG2 and RPA32 and we confirmed the importance of both UNG2 and RPA32 for optimal virus replication in a T cell line as well as in HIV-1 primary target cells. Even though macrophages and PBMCs (Peripheral Blood Mononuclear Cells), target cells of HIV-1, express low level of UNG2 and RPA32, these cellular proteins seem to be required for an efficient viral DNA synthesis leading to an optimal virus replication in primary cells. All these results suggest that Vpr controls the reverse transcription step through the recruitment of two cellular proteins UNG2 and RPA32 which allow the efficient dissemination of HIV-1 in the primary target cells
Nadeem, Muhammad Faisal. "Chaperone mechanism of the HIV-1 Gag and its promotion by the RPL7 host protein." Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ025.
Повний текст джерелаThe multidomain Pr55 Gag protein of HIV-1 plays a crucial role during late stages of viral replication, notably for the recognition and selection of genomic RNA as well as for the production of new viral particles. In addition to its structural role, Pr55 Gag also chaperones nucleic acid sequences, a property which is crucial for genomic RNA dimerization and annealing of the primer tRNA to the genomic RNA. Cellular partners like ribosomal protein RPL7 are thought to be recruited by Pr55 Gag to enhance its chaperoning potential. To investigate the nucleic acid annealing mechanism of Gag and RPL7, we examined their effect on the annealing reaction between dTAR, the DNA version of the viral transactivation element and its complementary cTAR sequence taken as relevant model HIV-1 sequences. Our data show that Gag and RPL7 exhibit different mechanisms for promoting the cTAR/dTAR annealing. When used together, RPL7 can help Gag to chaperone stable sequences of the genomic RNA that Gag would hardly be able to chaperone alone. This RPL7-driven boost in Gag chaperone activity is thought to be critical in the viral assembly process
Mittal, Seema. "Role of Protein Flexibility in Function, Resistance Pathways and Substrate Recognition Specificity in HIV-1 Protease: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/573.
Повний текст джерелаDai, Weiwei. "SERINC5: Its Sensitivity to Nef and Restriction of HIV-1." eScholarship@UMMS, 2018. https://escholarship.umassmed.edu/gsbs_diss/984.
Повний текст джерелаYakoob, Hena. "Influence of the Anti-HIV drug Elvitegravir on Chlamydial Development and the Characterization of Chlamydial Polymorphic Membrane Protein Expression in Herpes Simplex Virus (HSV)/C. trachomatis Co-infected Cells." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/honors/259.
Повний текст джерелаBuglione-Corbett, Rachel. "Adjuvant-Specific Serum Cytokine Profiles in the Context of a DNA Prime-Protein Boost HIV-1 Vaccine: A Dissertation." eScholarship@UMMS, 2013. https://escholarship.umassmed.edu/gsbs_diss/666.
Повний текст джерелаBuglione-Corbett, Rachel. "Adjuvant-Specific Serum Cytokine Profiles in the Context of a DNA Prime-Protein Boost HIV-1 Vaccine: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/666.
Повний текст джерелаSanterre, Maryline. "Étude de l'action sur l'épissage de protéines nucléaires se liant à la région de l'ARN du virus VIH-1 contenant le site d'épissage A7 et role de ces protéines sur d'autres sites accepteurs d'épissage de VIH-1." Thesis, Nancy 1, 2010. http://www.theses.fr/2010NAN10115/document.
Повний текст джерелаHIV-1 pre-mRNA splicing depends upon 4 donor and 8 acceptor sites, which are used in combination to produce more than 40 different mRNAs. To further characterize nuclear factors involved in these processes, we purified RNP complexes formed by incubation of SLS2-A7 transcripts in HeLa cell nuclear extracts by affinity chromatography to identify new associated proteins. We showed that, in addition to the well known hnRNP A1 inhibitor of site A7, nucleolin, hnRNP H and hnRNP K interact directly with SLS2-A7 RNA. We demonstrated that hnRNP K has multiple binding sites in the vicinity of site A7 and that binds cooperatively to hnRNP A1 to the A7 RNA region and limits the A7 utilization in vitro. As hnRNP A1 is a negative regulator of several HIV-1 splicing sites (A1, A2, A3), we tested whether hnRNP K may also reinforce hnRNP A1 inhibition at these sites. Surprisingly, hnRNP K activated in vitro splicing of the D1-A1, D1-A2 and D1-A3 introns. Interestingly, hnRNP K was found to reinforce strongly the ASF/SF2 activity at site A2, which indicates that depending on the splicing site hnRNP K can be a splicing activator or inhibitor. To test how hnRNP K influences the relative utilization of HIV-1 splicing sites in cellulo, we used plasmid p PSP containing all the HIV-1 splicing sites and tested the effect of over-expression in HeLa cells on alternative splicing of the PSP RNA. Doubling the amount of hnRNP K in HeLa cells led to a drastic change of the PSP RNA alternative splicing, which confirms the strong influence of hnRNP K on alternative splicing. Moreover, increase of cellular concentration of hnRNP K strongly decrease the viral Nef protein production. hnRNP K protein affects A7 splicing regulation but also regulates the majority of regulated splicing sites of HIV. By extension of the study of hnRNP K effect to other HIV-1 splicing sites, we discovered that hnRNP K is a general regulator of HIV-1 splicing
Basta, Beata. "Nouvelles molécules antivirales ciblant la protéine de la nucléocapside du virus VIH-1." Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-00868465.
Повний текст джерелаAkbay, Burkitkan. "Regulation of the Akt/mTORC1 Pathway by HIV Transcriptional Activator Tat in B Cells Modulation of mTORC1 Signaling Pathway by HIV-1 Production of Stable Cell Lines on the Basis of the Cultured RPMI 8866 B-Cells with Constant and Inducible Expression of the Human Immunodeficiency Virus Tat Protein HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells." Thesis, université Paris-Saclay, 2021. http://www.theses.fr/2021UPASL026.
Повний текст джерелаAggressive B cell lymphomas are the main cause of death in HIV-1 infected individuals, although B cells are not targeted by the virus. The exact mechanisms of the development of these lymphomas are not known. Previous studies of our team revealed that HIV-1 Tat can penetrate B cells, where it can induce ROS production, DNA damage and increase the chances of the oncogenic translocations specific for Burkitt lymphoma. In addition in many immune cells HIV-1 and its proteins (e.g. Tat) can regulate Akt/mTORC1 pathway, a central integrator of many intra and extracellular signals including viral infection and DNA damage. However, no studies have examined the regulation of Akt/mTORC1 pathway by Tat in B cells. In this thesis I have tested the hypothesis that HIV-1 Tat might produce oncogenic effects in B cells by modulating Akt/mTORC1 signaling pathway and regulating expression of genes involved in lymphomagenesis. I found that HIV-1 Tat activated Akt/mTORC1 signaling pathway, which leads to aberrant activation of AICDA (activation induced cytidine deaminase) due to inhibition of AICDA transcriptional repressors c-Myb and E2F8. These perturbations may ultimately lead to an increased genomic instability and proliferation that might cause B cell malignancies
Weiss, Eric R. "Investigating the Roles of NEDD4.2s and Nef in the Release and Replication of HIV-1: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/641.
Повний текст джерелаGonzalez, Daniel. "Les "phosphate binding protein" : entre import du phosphate et inhibition de la transcription virale." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4019.
Повний текст джерелаThe "phosphate binding protein" constitutes a family of proteins ubiquitously found in Prokaryotes but also more sparsely distributed in Eukaryotes. Involved in phosphate import, PBPs exhibits a well-characterized phosphate binding site with a peculiar hydrogen bond called "low barrier hydrogen bond" (LBHB). This LBHB is involved in the unique discrimination properties of PBPs, capable of discriminating phosphate from other similar anions such as arsenate of sulfate. Albeit this high discriminating property needs a high conservation of the phosphate binding pocket, different configurations are observed in nature. Herein, we have been interested in a PBP from a human pathogen, Clostridium perfringens, which presents an alternative phosphate binding site. Exhibiting a loss of the LBHB, C.perfringens PBP is the least discriminating PBP isolated so far. This weak discrimination property might be related to the environment of C.perfringens or to a functional adaptation of the PBP. On the other hand, PBPs issued from eukaryotic tissues exhibit HIV inhibition properties via a step not yet targeted in current therapies, i.e. the transcription. However, these proteins are difficult to obtain from human tissues and their expression in heterologous system remains impossible. We have developed a new methodology based on phylogeny in order to solubilise our study model, HPBP. Thus, we have obtained a soluble variant of HPBP which conserves the HIV-inhibiting properties. This unique tool both allow to unlock functional studies and lead to a better understanding on how PBPs are capable of inhibiting HIV
Fernández, Arauzo Leticia. "Péptidos sintéticos del GB virus C. Aplicación en el diagnóstico de infección y en el diseño de potenciales agentes terapéuticos contra el VIH-1." Doctoral thesis, Universitat de Barcelona, 2012. http://hdl.handle.net/10803/482076.
Повний текст джерелаGB virus C (GBV-C) (also formerly known as hepatitis G virus) is a non-pathogenic human virus. Its infection is more frequently in groups considered as high risk because it has similar routes of transmissions with other viruses such as hepatitis B virus, hepatitis C virus or human immunodeficiency virus (HIV). However, it is detected even in healthy people. There is a strong evidence for GBV-C association with ameliorated course of human immunodeficiency virus (HIV) disease, although its mechanism of action is yet to be determined. Thus, the study of the interaction between these viruses could give new therapeutic agents to HIV treatment. At present, there are no commercial systems to detect specific markers of GBV-C infection. In this thesis, the synthesis of branched peptide molecules was carried out by conjugating regions of the envelope protein E2 and the structural protein NS4 of the GBV-C virus. Afterwards, their antigenic capacity was evaluated. The ability of the synthesized molecules to inhibit cell fusion mediated by HIV-1 envelope protein was also studied in order to select potential inhibitors of virus entry into the cell. First of all, a detailed study of the E2 protein of GVB-C was carried out by preparing peptide microarrays with 124 linear sequences of this protein, using sera from patients infected with HIV-1 and healthy volunteers. Thus, potentially antigenic domains of the E2 protein of GBV-C were identified. After carrying out these assays and studying the accessibility profile of the potentially antigenic domain E2 (7-26), solid phase synthesis of linear, cyclic and branched peptides was carried out following an Fmoc/tBu strategy. Peptide constructions were characterized by HPLC, UPLC and mass spectrometry (ESI and MALDI-TOF) and purified by semipreparative HPLC. Subsequently, cell fusion assays were performed in order to evaluate the anti-HIV-1 activity of the peptide molecules derived from the N-terminal domain of the E2 protein of GBV-C. From this study, it could be concluded that the cyclic type constructions have a greater tendency towards a greater inhibition of HIV-1 entry in the cell. The ability to detect anti-GBV-C antibodies of all sequences and synthetic constructions were studied by the ELISA immunoenzymatic assay with sera from patients with chronic hepatitis C, patients undergoing hemodialysis, HIV-1 infected and sera from healthy volunteer donors. The results obtained demonstrated the potential diagnostic utility of the E2 region (7-26) of the GBV-C. Finally, the diagnostic value of the peptide domains identified by microarrays was evaluated with a panel of sera from patients infected with HIV-1. The combination of the peptide sequences studied allowed to establish a reactivity of 47% in the detection of anti-E2 antibodies of GBV-C in people infected with HIV-1. In addition, this technology has miniaturized the ELISA immunoenzymatic assay and it has demonstrated the usefulness of synthetic peptides as potential antigens for the development of a GBV-C infection diagnosis system.
Khoury, Georges. "Étude des mécanismes moléculaires régulant l'expression de la protéine TAT du virus de l'immunodéficience humaine, au niveau de la production de ses ARN messagers et de leur traduction." Thesis, Université de Lorraine, 2012. http://www.theses.fr/2012LORR0251.
Повний текст джерелаHIV-1 Tat protein is essential for viral replication. It allows the transcription of full-length viral RNAs, and due to its apoptotic properties it contributes to the AIDS disease. Hence, it is important to study the mechanisms regulating its production. Alternative splicing of the HIV-1 RNA, in particular, the use of acceptor sites A3 and A7 is required for tat mRNA production. Splicing at site A3 is highly regulated by cis-acting elements contained in a stem-loop structure SLS3A3, located downstream from site A3. By purifying RNP complexes formed in nuclear extract on a segment of the viral RNA containing site A3 followed by mass spectrometry analysis, we were able to highlight the binding of a new inhibitory protein, DAZAP1. Based on a set of ancient laboratory data and new results that I obtained, we have shown that SRSF7 protein, probably in synergy with SRSF1, limits the binding of DAZAP1 and splicing activation at site A3. We also showed that the viral protein Tat exerts a negative feedback control on tat mRNA production by restricting splicing activation of site A3 by SRSF7. The apical part of the stem-loop structure SLS3A3 (B motif) is highly conserved among HIV-1 strains. E Guittet team determined its 3D structure by NMR. The conformation of this apical loop is characteristic of stem-loop structures recognized by dsRBD proteins (double-stranded RNA binding domain). I was able to confirm this hypothesis by purifying RNP complexes formed by the B motif in nuclear extract. Thus, we have shown that the RNA dependent protein kinase (PKR), which plays in humans a major role in response to viral infection, is a partner of the B motif. By using chemical probes specific of the 2D structure of RNAs, I showed that the stem-loop structure SLS3A3 that contains the initiation codon of Tat is present in tat1 mRNA. We then developed a system to study the mechanisms regulating the initiation of translation of Tat protein. By using a bicistronic construct, I was able to confirm the existence of IRES activity in the 5?UTRtat1 region of tat1 mRNA, and define two segments that contain this activity. Preliminary results obtained with a bicistronic construct allowed us to begin testing the effect of different SR and hnRNP proteins on the activity of the IRES
Calao, Miriam. "Role of IkB kinase (IKK) complex post-translational modifications in NF-kB signaling and therapeutic applications for the treatment of HIV-1 infection." Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210318.
Повний текст джерелаCertains virus utilisent la voie de signalisation NF-κB afin de promouvoir leur propre réplication. C’est le cas du virus HIV-1 (Human Immunodeficiency Virus type 1), qui contient dans son promoteur deux sites de liaison pour NF-κB. Notre laboratoire a précédemment montré que l’utilisation du TNFα en combinaison avec la TSA, active l’expression virale de manière synergique. L’administration combinée d’un activateur du facteur NF-κB et d’un inhibiteur de désacétylases pourrait, en présence d’une thérapie anti-HIV-1 efficace, être envisagée dans le but d’éliminer les cellules réservoirs infectées de manière latente. L’utilisation thérapeutique du TNFα ou de la TSA étant inenvisageable en raison de leur toxicité, nous avons étudié l’effet d’autres substances ayant un plus grand potentiel thérapeutique et nous avons apporté une preuve de principe du potentiel thérapeutique de la coadministration de plusieurs activateurs viraux (inhibiteurs de HDACs[HDACIs]+inducteurs de la voie NF-κB) pour réduire le pool des réservoirs cellulaires infectés de manière latente.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished