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1
Swan, Christina Heidi. "HIV-1 intracellular immunization via HIV-1 derived vector delivered genetic mechanisms." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2006. http://wwwlib.umi.com/cr/ucsd/fullcit?p3204640.
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Thesis (Ph. D.)--University of California, San Diego, 2006.Title from first page of PDF file (viewed April 4, 2006). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
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Yang, Wa. "The evolution of HIV-1 and HIV-2." Thesis, University College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405605.
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LeÌtourneau, Sven C. "HIV-1 vaccine development." Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.442825.
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Haddrick, Malcolm. "HIV-1 RNA dimerisation." Thesis, University of Leicester, 1996. http://hdl.handle.net/2381/35383.
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Genomic RNA isolated from retroviral particles is a dimer composed of two identical strands. A region called the dimer linkage site close to the 5' end of the RNA may be involved in forming the dimer. Several models for the formation of the HIV-1 genomic RNA dimer have been proposed. In the "kissing loop" model, dimerisation results from base pairing between homologous sequences in an RNA stem loop. In the guanine tetrad model interstrand guanine contacts form the dimer. Mutations have been made preventing the dimerisation of subgenomic RNAs in vitro by these mechanisms. To prevent the "kissing loop" dimer forming the complementary loop sequence 711GCGCGC716 was changed to 711AAACGC716. To prevent the guanine tetrad dimer forming residue G819 was changed to U. These mutations were introduced into a clone of HIV-lNL4-3 separately and collectively. All three clones produced infectious virions. Dimeric RNA with similar thermal stabilities was isolated from viruses containing either the single or the double mutations. The results suggest that sequences involved in forming a guanine tetrad are not important for HIV-1 RNA dimerisation. In contrast sequences involved in forming a kissing loop complex are not absolutely required, but are important in forming a stable HIV-1 RNA dimer.
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Davis, Katie L. "Analysis of HIV-1 variable loop 3-specific neutralizing antibody responses by HIV-2/HIV-1 envelope chimeras." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2009r/davis.pdf.
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Duvall, Melody Gayle. "HIV-specific cellular immune responses in HIV-1 and HIV-2 infection." Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.441307.
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McIntyre, Glen J. Biotechnology & Biomolecular Sciences Faculty of Science UNSW. "Antiviral shRNA (for HIV-1)." Awarded by:University of New South Wales, 2006. http://handle.unsw.edu.au/1959.4/35215.
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Human Immunodeficiency Virus type I (HIV-1) is an RNA virus that causes Acquired Immunodeficiency Syndrome (AIDS). Gene therapy is a new treatment paradigm that aims to modify the patient???s cells with therapeutic agents to reduce viral replication and disease progression. A recently discovered technology with potential application in gene therapy for HIV-1 is the RNA interference (RNAi) pathway; a natural gene suppression mechanism where a 19 ??? 21 bp dsRNA trigger prevents the translation of complementary target RNAs. The RNAi pathway can be harnessed artificially with short hairpin RNAs (shRNAs or hairpins); expressed RNA transcripts that fold into ???hairpin??? configurations by virtue of selfcomplementary regions separated by a short ???loop??? sequence. The aim of this project was to use pre-clinical models to investigate shRNA design, construction, screening and coexpression for potential use as an anti-HIV-1 therapeutic agent. A PC2-rated assay using multiple fluorescent reporters was developed to screen shRNAs for anti-HIV-1 suppressive activity, simultaneously measuring, and distinguishing, between target-specific and nonspecific shRNA activities. Phi29 DNA polymerase was used to modify the primer extension method for constructing shRNA vectors, increasing its efficiency whilst maintaining its cost effectiveness. A novel sequencing procedure using a restriction enzyme loop sequence was developed, which allowed the sequence of all shRNA vectors to be confirmed at highthroughput automated sequencing facilities. A comprehensive study of hairpin design factors showed that whilst shRNA stem length could affect processing and activity, sequence composition was the critical determinant of suppressive activity. Using the screening and construction methods developed here, many hairpins were designed and tested with at least one highly active hairpin found for each HIV-1 gene. Pre-existing and novel shRNA co-expression strategies were successfully used to co-express up to 4 hairpins to theoretically counter the emergence of viral escape mutants. Overall, this work has shown that expressed shRNAs are potentially suitable to treat HIV-1, since highly active shRNAs can be designed against all HIV-1 genes, shRNA vectors can be efficiently constructed, shRNA activities can be effectively screened and shRNAs can be combined to suppress simultaneously multiple targets.
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Archer, John Patrick. "The diversity of HIV-1." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.495044.
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The phylogeny of the Human Immunodeficiency Virus type 1 (HIV-1) is characterized by extensive diversity. However when it comes to the persistence of the virus not all of this diversity is relevant. In this thesis I show that the significance of diversity, both In relation to epidemiology and vaccine design, varies within and between the HIV-1 groups. The substructure present within group O and at the center of the group M pandemic was observed to be similar to that found on random tree topologies, whereas the substructure present within globally sampled group M strains was significantly different.
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Brown, D. E. "Antisense approaches towards HIV-1." Thesis, University of Cambridge, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596956.
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Several forms of therapeutic antisense molecule have been developed. These include small interfering RNAs (siRNAs), short hairpin (shRNAs) and longer single stranded antisense RNAs. In this study, steric blocking RNA oligonucleotides (ONs) and their analogues were investigated. The packaging process of HIV-1 is highly specific and involves an interaction between the Gag protein and a conserved sequence that is only present on genomic viral RNA. This region is known as Ψ and comprises four stem loops (SL1-4), within which SL3 is a high affinity binding site for Gag. Deletion of SL3 severely reduces viral packaging. High affinity ONs targeted to Ψ inhibited Gag binding in vitro and confirmed SL3 as the major packaging determinant SL2 was also shown to influence Gag binding, but to a lesser extent. HIV-1 replication was inhibited following cellular delivery of SL3 targeted ONs. An ON targeted to trans-activating response region (TAR) of HIV-1 also showed antiviral activity in these assays. From those tested, mixmer ONs consisting of 2’-O-Methyl and locked nucleic acid analogues (2’Ome/LNA) showed significant and sequence-specific inhibition of viral replication. Having identified target sequences, viral vectors were developed to deliver expressed forms of these in vivo. A minimal lentiviral vector based on HIV-2 was produced with reduced homology to packaging constructs. This demonstrated efficient gene transfer.
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Heap, Caroline J. "Analysis of HIV-1 neutralisation." Thesis, University of Warwick, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409953.
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Ruggiero, Alessandra. "HIV-1 persistence during ART." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3003398/.
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Antiretroviral therapy (ART) suppresses HIV viremia, but it does not eliminate the stable cellular reservoir of integrated viral DNA that is generated early during infection. As a consequence, low levels of HIV are detected in patients with consistent viral suppression (HIV-1 RNA < 50 copies/ml) in CD4 cells in different body compartments including plasma, peripheral cells and CD4 T-cell subsets. We first explored the levels of HIV-1 RNA below the cut-off of clinical assay (HIV-1 RNA load < 50 copies/ml, herein referred to as 'residual viremia') in a group of patients who switched from Atripla to Eviplera due to toxicity. Furthermore, we studied HIV-1 DNA and RNA loads in peripheral blood of patients with stable virological suppression (HIV-1 RNA < 50 copies/ml) while being on first line-ART with 1 NNRTI and 2 NRTIs. The measured virological markers included the residual HIV-1 RNA load in plasma quantified by an ultrasensitive assay; total and integrated HIV-1 DNA in both peripheral blood mononuclear cells (PBMC) and the CD4 T-cell subsets using quantitative PCR methods; 2-LTR circular HIV-1 DNA in PBMC using droplet digital PCR assay. Furthermore, a panel of cellular and immunological markers of immune activation, as measured by flow cytometry and ELISA assay respectively, were available for the analysis. Additionally we explored alternative methods to quantify and to study HIV-1 persistence. In patients that switched from Atripla to Eviplera we observed that overall the patients showed maintained virologic suppression until the end of the observation; however, 4 patients experienced virologic rebound with HIV-1 RNA > 50 copies/ml and this was predicted by a progressive increase in residual HIV-1 RNA levels over time. Patients on suppressive ART were studied with a cross sectional approach and we observed detection of residual HIV-1 RNA and 2-LTR circular DNA in a proportion of patients and total HIV-1 DNA in PBMC the whole study group. Additionally, we found that residual HIV-1 RNA levels and total HIV-1 DNA were associated with sCD27 and CD8+HLA-DR/DP/DQ+ T-cells, respectively. Following setting-up of the Alu-gag qPCR assay, we measured integrated HIV-1 DNA in PBMC and we confirmed the association with CD8+HLA-DR/DP/DQ+ T-cells. In the context of assay development, we proposed the Alu-5LTR assay as an alternative to the Alu-gag assay for integrated HIV-1 DNA quantification and preliminary results showed increased sensitivity. Furthermore, we identified and characterized the tools needed to set up an in vitro system to study direct and cell-to-cell HIV-1 infection. Results from my thesis showed the importance of residual HIV-1 RNA monitoring to detect virus rebound. Moreover, patients on suppressive ART for a long period showed HIV detection in plasma and in cells which was associated with high levels of immune activation, suggesting a role for the host immune environment in HIV persistence. In the context of assay developments for more sensitive quantification of integrated HIV DNA reservoir, our proposed Alu-5LTR assay as described in this thesis may be a potential alternative.
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Mates, Jessica Marie. "TRANSCRIPTIONAL REGULATION OF HIV-1." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1395845500.
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Silva, Victor Barreto de Souza Brasil. "Co-infecção HIV-1/Tripanossomatídeos em macrófagos humanos efeito da infecção pelo HIV-1 e proteína Tat do HIV-1 sobre a replicação parasitária." reponame:Repositório Institucional da FIOCRUZ, 2009. https://www.arca.fiocruz.br/handle/icict/9114.
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Previous issue date: 2014-11-18Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil
Protozoários parasitos aparecem como co-patógenos em infecções pelo vírus da imunodeficiência humana (HIV)-1, resultando em um aumento mútuo na replicação viral e parasitária, e facilitando a progressão clínica de ambas as doenças. Os mecanismos pelos quais o HIV-1 induz um aumento na replicação do protozoário são desconhecidos. Neste trabalho, nós investigamos o papel do HIV-1 e da proteína trans-ativadora (Tat) do HIV-1 no aumento da replicação parasitária em macrófagos humanos primários co-infectados ou não com HIV-1 e Leishmania amazonensis ou com HIV-1 e Blastocrithidia culicis. Em alguns experimentos, macrófagos foram infectados somente com L. amazonensis ou B. culicis e expostos à proteína Tat recombinante do HIV-1. As replicações dos protozoários e do HIV-1 foram analisadas por índice endocítico ou ensaio imunoadsorvente ligado a enzima (ELISA) para p24, respectivamente. A infecção pelo HIV-1 dobrou a replicação da Leishmania em macrófagos, e soro contra o Tat do HIV-1 reduziu significativamente a replicação exacerbada do protozoário, indicando uma importante função desta proteína, a qual é liberada pelas células infectadas com HIV-1, neste processo. Corroborando estes resultados, a exposição de macrófagos infectados somente por Leishmania ao Tat recombinante (100 ng/mL) mimetizou a infecção pelo HIV-1. A multiplicação do protozoário diminuiu quando células infectadas por Leishmania foram tratadas com Tat na presença de anticorpos neutralizantes contra o Fator de Crescimento e Transformação (TGF)-b1, demonstrando a participação desta citocina no aumento da replicação da L. amazonensis em macrófagos. O tratamento com Tat induziu a expressão da enzima Ciclo-oxigenase (COX)-2 e a secreção de Prostaglandina E2 (PGE2), e o bloqueio da produção de PGE2 aboliu o aumento da replicação da Leishmania induzida por Tat Adição exógena de PGE2 estimulou o crescimento da Leishmania em macrófagos, e a neutralização imune de TGF-b1 abrandou este efeito. Analisados em conjunto, nós concluímos que Tat estimula a replicação da Leishmania via indução da síntese de PGE2 e conseqüentemente secreção de TGF-b1. Para avaliar se a infecção pelo HIV-1 desativa a atividade microbicida do macrófago, células infectadas com HIV-1 foram co-infectadas com um protozoário não patogênico (Blastocrithidia culicis), e nós observamos que a infecção pelo HIV-1 favoreceu a sobrevivência deste tripanossomatídeo. Por microscopia eletrônica, nós verificamos que tanto o HIV-1 quanto a B. culicis co-habitavam um mesmo macrófago, e que formas em divisão do protozoário podiam ser observadas no interior de macrófagos. De forma similar aos encontrados nos experimentos com Leishmania, o Tat ou o TGF-b1 dobraram o crescimento do protozoário em macrófagos infectados somente por Blastocrithidia. Em conclusão, nós identificamos, pela primeira vez, uma molécula do HIV-1 que promove a multiplicação de um protozoário patogênico (Leishmania), e permite a sobrevivência/crescimento em macrófagos humanos primários de um protozoário habitualmente não patogênico. Uma vez que a neutralização imune do Tat tem sido estudada como uma estratégia de vacinação contra o HIV-1, nossos resultados sugerem que a neutralização desta proteína também pode ser salutar no combate ao protozoário em casos de co-infecção
Protozoan parasites appear as human immunodeficiency virus (HIV)-1 co-pathogens, resulting in a mutuall enhancement of viral and parasite replication, and facilitating the clinical progression of both diseases. The mechanisms by which HIV-1 induces up-modulation of protozoan replication are unknown. In this work, we investigated the role of HIV-1 and HIV-1 transcriptional transactivator (Tat) protein in the enhancement of parasite replication in primary human macrophages co-infected or not with HIV-1. Human macrophages were co-infected with HIV-1 and either with Leishmania amazonensis or Blastocrithidia culicis. In selected assays, macrophages were infected only with L. amazonensis or B. culicis and exposed to recombinant HIV-1 Tat protein. Protozoan and HIV-1 replication were analyzed by endocytic index or p24 Enzyme Linked Immuno Sorbent Assay (ELISA), respectively. HIV-1 infection doubled the Leishmania replication in macrophages, and Tat antiserum significantly reduced the exacerbated parasite replication, pointing to a direct role of Tat protein released from HIV-1-infected cells in this process. Corroborating this finding, exposure of Leishmania-infected macrophages to recombinant Tat (100 ng/mL) mimicked HIV-1 infection. Protozoan replication diminished when Leishmania-infected cells were treated with Tat in the presence of neutralizing anti-Transforming Growth Factor (TGF)-b1 antibodies, showing a participation of this cytokine in the augmentation of L. amazonensis multiplication in macrophages. Interestingly, Tat induced the expression of the enzyme Cyclooxygenase (COX-2) and Prostaglandin E2 (PGE2) secretion, and blockage of PGE2 production abrogated the increased Leishmania replication induced by Tat. Exogenous addition of PGE2 elicited Leishmania replication in macrophages, and immunoneutralization of TGF-b1 blunted this effect. Taken together, we deciphered that Tat stimulates Leishmania replication via induction of PGE2 synthesis and consequently TGF-b1 secretion. To evaluate whether HIV-1 infection deactivates the microbicidal activity of macrophages, HIV- 1-infected cells were co-infected with a non-pathogenic protozoan (Blastocrithidia culicis), and we found that HIV-1 infection favors the survival of this trypanosomatid. By electron microscopy, we verify that both HIV-1 and B. culicis co-habited the same macrophage, and that dividing forms of the protozoan can be observed inside the macrophage. Similarly, Tat or TGF-b1 doubled the protozoan growth in Blastocrithidia-infected macrophages. In conclusion, we identified, for the first time, an HIV-1 molecule that promotes multiplication of a pathogenic protozoan (Leishmania) and permit survival of an otherwise non-pathogenic protozoan in primary human macrophages. Because immunoneutralization of HIV-1 Tat has been studied as a vaccination strategy against HIV-1, our results suggest that neutralization of this protein could be salutary in the combat against the protozoan in the cases of co-infection
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Soto-Rifo, Ricardo. "Translational control of HIV-1 and HIV-2 genomic RNA." Lyon, Ecole normale supérieure, 2010. http://www.theses.fr/2010ENSL0584.
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Les virus de la immunodéficience humaine de type 1 et 2 (VIH-1 et VIH-2) sont des pathogènes qui ont un grand impact sur la santé car plus de 33 millions de personnes sont infectées dans le monde. Les mécanismes qui contrôlent les étapes post-transcriptionelles de l’ARN génomique pendant les étapes tardives du cycle réplicatif ne sont pas très connu et donc les processus moléculaires qui permettent à l’ARN génomique de s’associer aux machineries cellulaires de traduction, transport ou dégradation restent à être déterminés. Dans ces travaux, nous avons contribué à améliorer notre connaissance sur les mécanismes qui contrôlent la synthèse des protéines à partir de l’ARN génomique de VIH-1 et VIH-2. Les résultats présentés dans ces travaux montrent que la structure d’ARN TAR joue un rôle primordial dans le contrôle des interactions de l’ARN génomique et la machinerie traductionnelle de la cellule. Nous montrons des données qui suggèrent une nouvelle étape lors du cycle réplicatif du VIH-2 dans laquelle l’ARN génomique est accumulé dans des granules cytoplasmiques avec des marqueurs des granules de stress. Nous mettons en évidence un mécanisme qui permettrait à l’ARN génomique du VIH-1 d’être exporté au cytoplasme et traduit de manière efficace grâce à l’helicase à ARN DDX3Infections by Human immunodeficiency viruses type-1 and type-2 (HIV-1 and HIV-2) have an enormous impact in Human health as more than 33 million people is living with HIV/AIDS worldwide. The mechanisms controlling post-transcriptional events during the HIV life cycle have just started to capture the attention of scientists and most of the molecular processes allowing the genomic RNA to interact with the host machineries for translation, transport or decay are still obscure or in way to be determined. In this work, we contribute to the progress in the knowledge of the mechanisms controlling protein synthesis from the HIV-1 and HIV-2 genomic RNA. Results presented here provide evidence for the TAR RNA structure as a key player in controlling the interactions between the HIV-1 and HIV-2 genomic RNA with the host translational machinery. We also provide data for a new step during the HIV-2 life cycle that involves the accumulation of the genomic RNA in cytoplasmic granules containing several stress granules components. Finally, we present evidence for a potential mechanism by which nuclear export and protein synthesis are linked during the HIV-1 replication cycle. As such, we show that DEAD-box RNA helicase DDX3, previously implicated in Rev-mediated nuclear export, is absolutely required for HIV-1 genomic RNA translation. We determined the TAR structure as the viral determinant required for DDX3 function in translation. Strikingly, we also showed that DDX3 is specifically required for HIV-2 and SIV translation but not for FIV, HTLV-1, MLV or Line-1 suggesting that this function was acquired during primate lentiviruses evolution. Taken together, results obtained during this work highlight several key aspects of the HIV-1 and HIV-2 genomic RNA post-transcriptional control that may be critical for viral replication
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Reinberger, Stefanie. "Phänotypische Charakterisierung des viralen Hüllproteins (Env) von HIV-1 durch Konstruktion rekombinanter HIV-1-Varianten." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=964611155.
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Winstone, Nicola. "Characteristics of HIV-1 specific T cell responses in healthy, HIV-1 negative vaccine recipients." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491609.
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It is estimated that there are currently 42 million individuals living today with human immunodeficiency virus-l (HIV-1) infection. Highly active anti-retroviral therapy (HAART) is the only treatment available to date, which reduces viral load and delays progression to acquired immunodeficiency syndrome (AIDS), but adherance can be a challenge due to side effects caused by drug toxicity, its cost if medication. is not free, and the complicated regimen involved (Akileswaran, Lurie et al. 2005). Resistant mutant strains evolve after long term therapy (Vaclavikova, Weber et al. 2005). These expensive drugs are not available for social and economic reasons to 80% of infected individuals in . the developing world (UNAIDS 2004). A vaccine to this virus will probably be the most effective method of stemming the pandemic (McMichael and Hanke 2002). Correlates of protection to induce sterilizing .immunity against HIV infection, or to control viral replication and prevent transmission· during chronic infection are as yet, unknown. However an association has been observed between long term non progression to disease, and the presence of functional HIV specific T cell responses. A novel Clade A HIV-l vaccine was designed to elicit T cell responses, delivered as pTH.HIVA or MVA.HIVA and has been trialled in HIV negative humans over the last 5 years. Results of the most recent clinical trials are presented, using sensitive T cell assays optimised in this study. The longevity, functional and phenotypic properties of HIV specific T cells generated by vaccination were examined. The most immunogenic vaccine regimen was observed using a pTH.HIVA DNA prime, followed by a pox virus vectored boost. mvA specific memory T cells that produced IFN-y as measured in a cultured ELISPOT, were detectable in 50% of individuals who had received vaccine up to 3 Yz years previously. These cells expanded in culture and produced anti-viral cytokines and chemokines. Through understanding the quality of vaccine induced populations of cells with regards to potential antiviral function, we may progress towards designing a HIV vaccine and immunisation schedule that will be efficacious in stemming the global pandemic.
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Yilmaz, Alper. "Translational control of mRNAs transcribed from HIV-1 provirus and HIV-1 based lentiviral vectors." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1189785802.
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Chen, H. K. Jonathan. "Molecular epidemiology of HIV-1 and characterization of drug resistant HIV-1 in Hong Kong." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B39634401.
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Bates, Matthew Adam. "Betaherpesvirus genetic variation and infection in HIV-1 infected and 'HIV-1 exposed' Zambian children." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2010. http://researchonline.lshtm.ac.uk/4646542/.
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The betaherpesviruses human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV-6) are investigated here as pathogens in Zambia, an HIV -1 endemic region where there was little previous data. In particular we assess the effects of these viruses on 'maternally HIV-l exposed' infants: HIV-l negative infants of HI V-I positive mothers. HCMV and HHV-6 are serious causes of morbidity and mortality in HIV / AIDS and are linked with AIDS progression, so in this thesis they are investigated in both HIV -1 infected and uninfected Zambian children, along with maternally HIV exposed infants, an under studied and growing group in Southern Africa. The aim ofthis thesis is to employ qualitative and quantitative PCR assays to determine betaherpesvirus prevalence, loads and genotypes in three independent Zambian paediatric cohorts: Two retrospective cohorts (141 infants hospitalized with fever and 36 childhood HIV-1 positive respiratory mortalities), and also one prospective cohort (812 infants taking part in a population-based study designed to test the efficacy of a micronutrient fortified feed supplement to improve growth and health) in which relationships between betaherpesvirus infection, duration of breast feeding, infant growth and morbidity were investigated. Prevalence and loads were highest within the symptomatic cohorts, although lower levels of both viruses were also detected in sera from healthy infants taking part in the prospective study. High load HCMV infections were shown here to be significantly more prevalent in maternally HIV -1 exposed infants. Genotyping analysis focused of two hypervariable glycoproteins (gO and gN), which in HCMV have been shown to form seven linked genotypes. Here we identified a new genotype (gN4d) and demonstrated linkage with g05, demonstrating now eight gO/gN linkages. Analyses of this data and that generated in other countries show these linkages are globally maintained. Conversely for HHV -6, whilst HHV-6B is the predominant strain for childhood infections in the V.S, Europe and Japan, in Zambia HHV-6A was identified in 84% ofinfant infections, suggesting emergence elsewhere. The prevalence of active betaherpesvirus infections through detection of viral sera-DNA was 34-40% for HCMV and 8-13% for HHV-6, showing that primary infection with HCMV occurs much earlier in this region than in European and North American countries. Active HCMV infections were associated with inhibitory effects on growth and a trend for increased morbidity in HIV -1 exposed infants as measured by an increased rate of hospital referrals. HCMV seroprevalence was associated with anaemia and stunting, and breast feeding increased HCMV transmission, particularly in HIV -1 exposed infants. A micronutrient supplement with iron reduced anaemia. In summary, genotypes of HCMV and HHV-6 were identified and characterised in infant infections in this region, and analyses shows association with morbidity and growth delays for HCMV infected children, particularly with maternal HIV -1, a newly identified potential hazard for this population.
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Wang, Bin. "Molecular mechanisms in human immunodeficiency virus type-1 (HIV-1) pathogenesis and mother to child transmission of HIV-1." Thesis, The University of Sydney, 1996. https://hdl.handle.net/2123/27541.
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This thesis is divided into three parts (1) the mechanisms by which HIV—1 generates genetic diversity in vivo to escape the human immune system and generate a hybrid genome, (2) the viral factors responsible for long-term survival of HIV-1 infected patients, and (3) the molecular mechanisms in HIV-1 transmission from mother to child and also non—transmission.
Recombination has long been known to represent an important means by which retroviruses genetic diversity. Recombination between HIV- strains involving divergent strains has been previously reported, but so far, the in vivo recombinational events between closely related HIV-1 strains/variants (belonging to the same subtype) have been difficult to detect. If the recombination is happening between closely related strains or within the same subtypes of HIV-1, it may pose a threat to designing of subtype based vaccines for HIV-1 control.
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Han, Wenlong. "Interference with HIV-1 primer selection by siRNA directed to the HIV-1 primer binding site." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2006. https://www.mhsl.uab.edu/dt/2007r/han.pdf.
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Rutbemberwa, Alleluiah. "Characterisation of HIV-1-Specific CD8+t Lymphocyte immune responses in HIV-1 infected Ugandan individuals." Thesis, Imperial College London, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289822.
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Chen, Renxiang. "Studies of HIV-1 mutagenesis during drug therapy and the molecular determinants of HIV-1 variation." Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1092663963.
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Thesis (Ph. D.)--Ohio State University, 2004.Document formatted into pages. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2005 Aug. 16.
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Naghavi, Mojgan H. "Regulation of HIV-1 provirus transcription /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4865-8/.
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Chen, Nan. "The role of HIV-1 Nef gene in HIV-mediated pathogenesis." Thesis, University of Oxford, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404289.
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Watkins, Gemma L. "A comparison of HIV-1 and HIV-2 gag gene expression." Thesis, University of Warwick, 2012. http://wrap.warwick.ac.uk/45902/.
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Despite being closely related viruses with similar replication cycles, HIV-2 replicates more slowly than HIV-1 and produces fewer particles, resulting in a lower plasma viral load. Expression of the major structural gene, gag, from HIV-1 and HIV-2 proviruses was compared to investigate whether this could play a role in the difference in particle production observed between HIV-1 and HIV-2 infection. Using quantitative RT-PCR, significantly less full-length HIV-2 gag mRNA was found to be transcribed from its provirus than for HIV-1. Sub-cellular fractionation allowed us to determine HIV-1/2 gag mRNA levels in the nucleus and cytoplasm throughout a time course. RNA export of HIV-2 gag mRNA was shown to be slower than for HIV-1 gag mRNA. HIV-2 full-length gag RNA was shown to be translated much less efficiently than HIV-1 in a range of cell lines. Both HIV-1 and HIV-2 Gag have been proposed to be translated by internal ribosome entry. Shutting down capdependent translation (by poliovirus-mediated eIF4G cleavage) significantly reduced translation from both HIV-1/2 gag RNAs, with no evidence of compensatory IRES activity. This suggests that cap-dependent translation is the predominant mechanism for translation of both HIV-1 and HIV-2 RNA. Additional work explored HIV RNA-protein interactions by UV cross-linking experiments using cellular proteins. Several proteins differentially binding to HIV-1/2 5’ UTR RNAs were identified and, in particular, a 45 kDa protein binding only to the HIV-1 5’ UTR. Attempts were made to characterise the proteins binding with different affinities to HIV-1 and HIV-2 RNAs. Confocal microscopy was used to visualise HIV-1/2 Gag expression within the cell. Both HIV-1 and HIV-2 Gag expression was shown to be reduced when siRNA was used to inhibit the cellular clathrin adaptor protein AP-1. In conclusion, HIV-2 Gag gene expression was found to be less efficient than HIV-1 at the level of transcription, RNA export and translation. Future work will continue to investigate the mechanisms behind these differences.
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Cleveland, S. Matthew. "HIV-1-specific antibody responses to a plant virus-HIV chimera." Thesis, University of Warwick, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340090.
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Rocafort, Juncà Muntsa. "Gut microbiome in HIV-1 infection." Doctoral thesis, Universitat Autònoma de Barcelona, 2018. http://hdl.handle.net/10803/666775.
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Una vegada el Virus de la Immunodeficiència Humana tipus 1 (en anglès HIV-1) infecta l’organisme hoste es produeix una ràpida i severa destrucció del teixit limfoide associat a tracte gastrointestinal que inclou, entre d’altres, significants pèrdues cel·lulars del sistema immunitari i epitelial de l’hoste. Seguidament es produeix un increment de la permeabilitat de la paret intestinal que permet la translocació microbiana. Així i doncs, productes i cèl·lules microbianes que normalment queden confinats i controlats dins la llum intestinal ara poden travessar l’epiteli intestinal i entrar en circulació sanguínia convertint-se en un nou focus d’activació immunitària i inflamació. Per la seva significant contribució en la patogènesis del HIV-1, gran part de la recerca en microbioma dels últims anys s’ha centrat en entendre els canvis que tenen lloc en les comunitats microbianes que habiten dins l’intestí humà després de la infecció per HIV-1 i de l’inici de tractament antiretroviral (en anglès ART).
Els primers estudis transversals van descriure relacions contradictòries entre la riquesa i diversitat microbiana a l’intestí i la infecció per HIV-1 i van suggerir una substitució de Bacteroides per Prevotella com a conseqüència de l’adquisició viral. Aquests resultats però, no s’han confirmat ni en models animals ni en estudis balancejats per grups de risc de transmissió de VIH-1. En estudis en models de primats no humans la infecció pel virus de la immunodeficiància de simi s’ha associat a una expansió de les comunitats víriques intestinals però no s’ha descrit un canvi consistent en les comunitats bacterianes.
En dues cohorts europees independents de persones amb infecció crònica per HIV-1 i persones no infectades de Barcelona (n=156) i Estocolm (n=84), els individus homosexuals (en anglès MSM), presentaven una microbiota intestinal més rica i diversa i una major abundància relativa de Prevotella, en comparació amb individus heterosexuals (no-MSM) que estaven enriquits per Bacteroides, independentment de la infecció per HIV-1. Estratificant els grups d’estudi en funció de la seva preferència sexual (MSM vs non-MSM), individus infectats amb HIV-1 presentaven valors inferiors de riquesa i diversitat bacteriana, amb els valorsmés baixos en el grup de individus amb una resposta discordant a ART. Tot i així no hi havia canvis evidents respecte una disbiosi específica de infecció per VIH-1. En la nostra cohort d’estudi de Barcelona, la dieta tenia un efecte limitat sobre la composició de la microbiota intestinal.
Per estudiar els efectes longitudinals de la infecció per HIV-1 en la microbiota intestinal, vam fer un seguiment de 9-18 mesos a 49 persones de Moçambic diagnosticades amb infecció recent per HIV-1 i 54 persones no infectades, i les vam comparar amb dos grups de persones amb infecció crònica per HIV-1, tan si estaven amb ART (n=27) o no (n=71). En aquest estudi, seguint la infecció recent per HIV-1, es produïa una major secreció d’Adenovirus en femta, la qual persistia en infecció crònica i no desapareixia amb l’administració de ART. Paral·lelament també vam descriure canvis transitoris no específics en la riquesa i la composició bacteriana després de la infecció recent per HIV-1. Malgrat certa resiliència inicial al canvi, sí que s’evidenciava una signatura en quan a composició bacteriana en individus amb infecció crònica per HIV-1. Aquesta signatura, que incloïa pèrdua de Akkermansia, Anaerovibrio, Bifidobacterium i Clostridium, ja ha estat prèviament associada a inflamació crònica, anergia de limfòcits T CD8+ i desordres metabòlics.
En conclusió: 1) La preferència sexual és un factor de confusió important que s’hauria de considerar d’ara endavant, especialment en estudis de microbioma intestinal i HIV-1; 2) La microbiota intestinal sembla ser inicialment resilient a canviar després la infecció per HIV-1 però amb el pas del temps i progressió a fase crònica sí que apareix una signatura bacteriana amb perfil pro-inflamatori; i 3) Els canvis en la microbiota intestinal no només afecten les comunitats bacterianes sinó també, com a mínim, les comunitats víriques.Soon after Human Immunodeficiency Virus type 1 (HIV-1) infection, a severe and rapid depletion of the gut-associated lymphoid tissue occurs, including significant loss of both, immune and epithelial host cells. This is followed by an increased permeability of the intestinal cell lining which facilitates microbial translocation. Microbial cells and products that are usually contained and controlled within the intestinal lumen, can now circulate in the bloodstream and become a new source for immune activation and inflammation. Because of the significant immune imbalance in the GALT after HIV-1 infection, recent microbiome research has focused on understanding the changes occurring in the microbial communities inhabiting the human gut after HIV-1 perturbation and in response to antiretroviral treatment (ART). Initial cross-sectional studies provided contradictory associations between gut microbial richness and diversity and HIV-1 infection and suggested shifts from Bacteroides to Prevotella predominance following viral infection. Nonetheless, these results have not been confirmed in animal models or in studies matched for HIV-1 transmission risk groups. For instance, in non-human primate models Simian Immunodeficiency Virus infection is followed by expansion of enteric virome but has a limited impact on the gut bacteriome. In two independent European cross-sectionals cohorts of chronically HIV-1-infected subjects and uninfected controls, in Barcelona (n=156) and Stockholm (n=84), men-who-have-sex-with-men (MSM) showed a Prevotella-enriched gut microbiota and higher microbial richness and diversity compared to non-MSM individuals who predominantly showed a Bacteroides-enriched microbiota, regardless of HIV-1 infection. After stratifying for sexual orientation (MSM vs. non-MSM), we described lower microbial richness and diversity in HIV-1 infected subjects, more so in subjects with an immune-discordant response to ART, but there was no solid evidence of an HIV-1-specific dysbiosis. In our Barcelona cohort, diet did not have a major impact on gut microbiota composition. To understand the longitudinal effects of HIV-1 infection on the human gut microbiota, we prospectively followed 49 Mozambican subjects diagnosed with recent HIV-1 infection and 54 uninfected controls for 9-18 months and compared them with 98 chronically HIV-1-infected subjects ART-treated (n=27) or not (n=71). Recent HIV-1infection was characterized by increased fecal Adenovirus shedding, which persisted during chronic HIV-1 infection and did not resolve with ART. Recent HIV-1 infection was also followed by transient non-HIV-1-specific changes in the gut bacterial richness and composition. Despite early resilience to change, an HIV-1-specific signature in the gut bacteriome could be eventually identified in chronically HIV-1-infected subjects. Such signature featured depletion of Akkermansia, Anaerovibrio, Bifidobacterium, and Clostridium, and has been previously associated with chronic inflammation, CD8+ T-cell anergy and metabolic disorders. In conclusion: 1) Sexual practice is an important confounding factor in microbiome studies that needs to be considered, especially in HIV-1-gut microbiota studies; 2) Gut microbiota is initially resilient to change right after HIV-1 acquisition but a pro-inflammatory-bacterial signature eventually appears in chronic phases of the infection, and 3) Changes on the gut microbiota do not only impact bacterial communities, but, at least, also viral communities.
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Jauer, Christin Mariel. "Analyse eines unterquantifizierten HIV-1-Isolats." Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-125031.
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Groot, Fedde. "Dendritic cell-mediated hiv-1 transmission." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2006. http://dare.uva.nl/document/36281.
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Kjerrström, Zuber Anne. "Enhancement of HIV-1 DNA immunogens /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-304-x.
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Alaeus, Annette. "Significance of HIV-1 genetic subtypes /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3434-7/.
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Enting, Roeline Henny. "Neurological manifestations of HIV-1 infection." Rotterdam : Amsterdam : R.H.Enting ; Universiteit van Amsterdam [Host], 2000. http://dare.uva.nl/document/56445.
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Beerens, Nancy. "Regulation of HIV-1 reverse transcription." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/65252.
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Abdurahman, Samir. "Studies on HIV-1 core assembly /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-363-4/.
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Solis, Mayra. "Immune evasion mechanisms by HIV-1." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103531.
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Induction of the innate immune response by viral pathogens is characterized by a rapid production of Type I interferons (IFNβ/α). Recognition of viral components by Toll-like receptors (TLRs) or RIG-I-like receptors (RLRs), initiates multiple intracellular signalling cascades that culminate in the activation of the transcription factor NF-B and the interferon regulatory factors-3 and 7 (IRF-3 and IRF-7). As a consequence, these events lead to the production of immunoregulatory molecules, including Type I IFNs, pro-inflammatory cytokines and IFN-stimulated genes (ISGs), resulting in the inhibition of virus replication. Throughout evolution, viruses have developed strategies to subvert the innate immune response for their own benefit. Human immunodeficiency virus type-1 (HIV-1), the etiological agent of the acquired immunodeficiency syndrome (AIDS), has been shown to evade the innate immune response, resulting in disease progression. Thus, understanding the distinct mechanisms by which HIV-1 modulates TLRs and RLRs signaling pathways will ultimately lead to the development of novel strategies to inhibit HIV-1 replication and propagation. Studies have indicated that TLRs that signal via NF-B enhance HIV-1 replication. However, TLR4 stimulation triggers both NF-B and the IFN pathway and thus may have inhibitory effects on HIV-1 replication. Our first study was aimed at better understanding the role of TLR4 in HIV-1 replication. Therefore, we first characterized IRF-3 and IRF-7 activation following TLR4 stimulation. Our results demonstrate that the non-canonical TBK1 and IKKε are activated with distinct kinetics resulting in the activation of IRF-3 and subsequent induction of Type I IFNs. Thus, activation of the IFN pathway via TLR4 stimulation can provide a novel strategy to inhibit HIV-1 replication. Our second study sought to further delineate the different signaling pathways activated by HIV-1. Accordingly, transcriptional changes induced by distinct HIV-1 subtypes in immature dendritic cells were examined by microarray analysis. Our findings demonstrate that during the late phase of HIV-1 infection, a subset of genes is differentially regulated by the subtypes. In addition, this study highlights the important role of immature dendritic cells in HIV-1 replication and dissemination. Finally, given the importance of RLRs in the recognition of RNA viruses, the objective of the final study was aimed at investigating the evasion mechanisms employed by HIV-1 to counteract the initial antiviral response. Our results reveal that HIV-1 RNA is detected by the cytosolic receptor RIG-I. However, the HIV-1 viral protease sequesters RIG-I to the lysosomes and thus inhibits RIG-I-mediated antiviral response. Overall, the research presented in this thesis provides new avenues for developing novel therapeutic and preventive strategies to combat HIV-1/AIDS.L'induction de la réponse immunitaire innée par des pathogènes viraux est caractérisée par une production rapide des interférons de Type I (IFNβ/α). Les Toll-like (TLR) ou RIG-like (RLR) récepteurs détectent divers composants viraux induisant multiples voies de signalisation intracellulaire impliquées dans l'activation du factor de transcription-NF-B- ainsi que des facteurs de régulation de l'interféron-3 et -7 (IRF-3 et IRF-7). Ces évènements mènent à la synthèse de molécules immunorégulatrices, tel que les interférons (IFN) de Type I, les cytokines pro-inflammatoires et les gènes stimulés par l'IFN (ISG), qui jouent un rôle important dans l'inhibition de la réplication virale. Au cours de l'évolution, les virus ont développé des stratégies pour contrer la réponse immunitaire innée afin de se répliquer. Le virus de l'immunodéficience humaine de type 1(VIH-1), l'agent infectieux du syndrome de l'immunodéficience acquise (SIDA), échappe à la réponse immunitaire innée, ce qui favorise la progression de la maladie. Par conséquent, une meilleure compréhension des mécanismes par lesquels le VIH-1 module les voies de signalisation des TLR et des RLR pourrait mener au développement de nouvelles stratégies thérapeutiques pour empêcher la réplication et donc la propagation du VIH-1. Des études ont démontré que les TLR qui signalent par l'intermédiaire de NF-B augmentent la réplication du VIH-1. Cependant, la stimulation du TLR4 déclenche à la fois la voie de signalisation de NF-B et celle des IFN, pouvant avoir ainsi des effets inhibiteurs sur la réplication du VIH-1. L'objectif de notre première étude était de comprendre le rôle du TLR4 dans la réplication du VIH-1. Par conséquent, nous avons caractérisé la voie d'activation des IRF-3 et IRF-7 suite à la stimulation du TLR4. Nos résultats démontrent que les kinases non-canoniques TBK1et IKKε sont activées avec une cinétique distincte ayant pour conséquence l'activation de l'IRF-3 et l'induction subséquente des IFN de type I. Par conséquent, l'activation de la voie de signalisation des IFN par la stimulation du TLR4 pourrait offrir une nouvelle stratégie pour inhiber la réplication du VIH-1. Notre deuxième étude a eu pour but de définir les différentes voies de signalisation activées par le VIH-1. Les changements transcriptionels induits par les différents sous-types du VIH-1 dans les cellules dendritiques immatures ont été examinés par analyse de microréseaux. Nos résultats démontrent que pendant la phase tardive de l'infection VIH-1, un ensemble de gènes est différemment régulé par les différents sous-types du VIH-1. En plus, cette étude accentue le rôle important des cellules dendritiques immatures dans la réplication et la dissémination du VIH-1. En conclusion, étant donné l'importance des RLR dans la reconnaissance des virus à ARN, l'objectif de la dernière étude a été d'étudier les mécanismes d'évasion utilisés par VIH-1 pour contrer la réponse antivirale innée. Nos résultats démontrent que l'ARN du VIH-1 est détecté par le récepteur cytosolique RIG-I. Cependant, une protéine du VIH-1 -la protéase- séquestre le récepteur RIG-I dans les lysosomes et empêche l'activation de la réponse antivirale initié par le récepteur RIG-I. De façon générale, la recherche présentée dans cette thèse propose de nouvelles avenues pour développer des stratégies préventives et thérapeutiques afin de combattre le VIH-1/SIDA.
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Chong, Sannie Siaw Foong. "Anisotropic potential HIV-1 protease inhibitors." Thesis, University of Hull, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327289.
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Fiore, Simona. "HIV-1 infected women in Europe." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1444410/.
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This thesis aims to describe the wider impact of HIV infection on reproductive choices and pregnancy outcomes in HIV-infected women in Europe. Characteristics of 403 HIV-infected women enrolled in a survey on reproductive choices are described. There was no evidence to suggest HIV-infected women have problems to conceive maternal well-being, an uninfected partner and not having children yet were strongly associated with being pregnant. Results from a laboratory-based descriptive study, including 57 pregnant women provide a biological explanation for HAART-associated premature delivery in HIV- infected women cytokine patterns (IL2 and IL10) were analysed over three trimesters of pregnancy and in relation to gestational age at delivery. Intrauterine growth (femur length, head and abdominal circumference) of infants born to 316 HIV infected mothers, compared to an uninfected population is reported. The average z-score of head circumference and femur length in HIV- infected women was below the reference (32th centile and 15th centile respectively), but the average z-score for abdominal circumference differs only marginally (49th centile). In order to add one more piece of information in relation to maternal treatment and gestational age at delivery, birth-weight from a large European cohort was analysed and compared to the British standard. Mean z-scores decreased from - 0.10 (46th centile), -0.13 (45th centile) and -0.30 (37th centile) throughout gestation indicating that children born to HIV infected mothers became smaller towards the end of pregnancy, and premature delivery in HAART-treated mothers was not associated to fetal distress. Complications after delivery according to infection status of the mother and mode of delivery, were reported from a total of 250 HIV-status matched pairs delivered vaginally and from 158 by elective caesarean section. HIV-infected women suffered an increased risk of minor complications, but major complications only occurred in the caesarean section arm.
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Kong, Leopold. "HIV-1 gp120 : flexibility and glycosylation." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.533859.
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Krashias, George. "Adjuvant for vaccination against HIV-1." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.531970.
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Forte, Serene E. "Envelope Determinants of HIV-1 Cytopathicity." eScholarship@UMMS, 1998. http://escholarship.umassmed.edu/gsbs_diss/190.
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In vivo infection with HIV-1 is typically characterized by progressive clinical and immunological deterioration associated with a decrease in CD4 T-cells. The mechanism of CD4 T-cell depletion in vivo and its role in HIV-1 pathogenesis and development of AIDS is not well understood.
My research has focused on understanding the mechanism or mechanisms by which HIV-1 induces cell death. To address this aim, a panel of primary HIV-1 isolates were characterized in vitro for replication kinetics, syncytium formation, and cytopathic effects. From this panel two viral isolates, one from patient A and the other patient D, were selected for further evaluation. Patient A was asymptomatic with absolute CD4 cell count of 2302 at the time of virus isolation and remains so nine years later. Patient D was symptomatic with absolute CD4 cell count of 64 and has subsequently died from AIDS. Both of these patients maintained high viral load in vivo. When the viruses were examined in vitro, they also replicated to high titers. However, there were dramatic differences regarding the induction of cell death by HIV-1 isolates. Viruses obtained from patient A did not induce cell death although they replicated to high titers. In contrast, viruses obtained from patient D were extremely cytopathic in PBMCs with comparable viral replication. Therefore, viral replication alone does not predict the single-cell killing capacity of primary HIV-1 isolates. HIV-1 viruses isolated from an individual with normal CD4 T-cell numbers and an individual with CD4 T-cell depletion replicated to equivalent levels in primary CD4 T-cells. However, the virus isolated from the symptomatic individual induced cell death and the virus isolated from the asymptomatic individual was non-cytopathic in vitro.
It is known that HIV-1 exists in the host as a group of related viruses known as quasispecies. This diversity allows the virus a broad spectrum of genotypes which result in multiple phenotypic properties. It follows then that a single viral isolate may contain a number of variants which differ in their ability to form syncytia, cell tropism, replication kinetics, as well as cytopathic potential. To address this, biological clones were obtained from each of the patients viral quasispecies and characterized for replication and cytopathicity. These clones, GC6 8-4 (isolated from patient A) and HC4 (isolated from patient D) maintained the same viral phenotype as the parental virus. In other words, HIV-1 biological clone GC6 8-4 was non-syncytium inducing (NSI) and non-cytopathic in vitro. In contrast, HIV-1 biological clone HC4 was syncytium inducing (SI) and cytopathic in vitro.
It has been reported that the envelope gene of HIV-1 contains the major determinants of HIV-1 induced CD4 T-cell depletion (17). To understand what may be responsible for the differences in cytopathic behavior between the biological clones, GC6 8-4 and HC4 (42), I analyzed their envelope genes. Chimeric viruses were constructed by switching env regions from V2 through V3 of the biological clones with the corresponding region from the molecular clone NL4-3. These HIV-1 chimeric viruses exhibited similar replication kinetics as well as syncytium inducing abilities. The chimeric virus containing the env region of biological clone, GC6 8-4, was NCP in the single cell killing assay, while the chimeric virus containing the env region of biological clone, HC4, was CP in the single cell killing assay. These studies suggest the presence of a cytopathicity determinant which maps to the envelope region downstream from V2 and through V3 (Stu I at position 6822 to Nhe I at position 7250 based on NL4-3 sequence (101)).
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McClure, Charles Patrick. "HIV-1 in the genital tract." Thesis, University of Nottingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275163.
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Bristow, Richard G. W. "Antibody recognition of HIV-1 glycoproteins." Thesis, Open University, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315370.
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Mok, Hoi Ping. "Proviral gene expression of HIV-1." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.614281.
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Lockett, Sarah. "Factors affecting heterosexual HIV-1 transmission." Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/12452.
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The aim of this thesis was to investigate a broad variety of factors, in a cohort of EU heterosexual partners of HIV+ individuals (indexes), which may affect heterosexual transmission. The immune function of the EUs was assessed and compared to normal controls, by monitoring proliferative responses to mitogen, recall and alloantigens and a combination of recombinant HIV proteins. Cytokine responses to these stimuli were also monitored. The EUs were also confirmed to be uninfected by polymerase chain reaction (PCR). The EUs had similar proliferative responses to controls for both the allogenic and recall antigens and showed a minor difference in the response to the mitogen, phytohaemagglutinin (PHA), which may reflect differences in the kinetics of the response. An increase in the amount of interferon-γ (IFN-γ) produced in response to alloantigen was seen in EUs compared to controls, which could potentially inhibit HIV replication. The proportion of lymphocytes expressing the MHC Class II protein, human leucocyte antigen-DR (HLA-DR), was also elevated in the EUs compared to controls and may reflect an overall increase in the activation status of the EU' lymphocytes. Genetic factors which were investigated included the HLA antigens and the recently reported mutations in the CC chemokine receptors (CCR), CCR-2 and CCR-5, utilised by certain strains of HIV as co-receptors for entry. The HLA allele DR5 was elevated in frequency in the EU cohort compared to population controls and to HIV+ individuals who were infected by heterosexual exposure.
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Vigan, Raphael. "Cellular targets of HIV-1 VPU." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/cellular-targets-of-hiv1-vpu(14764437-266c-4b94-b53e-1a7a7e6ea2a9).html.
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Aside from the typical retroviral gag, pol, and env genes, HIV-1 encodes a set of accessory proteins. Amongst those, Vpu modulates the expression of several cell surface receptors within the infected cell to promote HIV-1 replication. Particularly, Vpu enhances virus release by overcoming the antiviral action of tetherin. HIV-1 is not the only virus to have evolved countermeasures to inactivate tetherin. Here we have investigated the strategy employed by Kaposi’s sarcoma-associated herpesvirus (KSHV) to escape from tetherin-mediated restriction of virus particle release. We have found that KSHV encodes a ubiquitin ligase, K5, that ubiquitinates tetherin on its cytoplasmic tail to target it for endolysosomal degradation. We then assessed the determinants in the Vpu transmembrane domain required to antagonize tetherin. Three amino acid residues that form one face of the transmembrane region of Vpu were found to be important for the interaction with tetherin. In contrast to Vpu from HIV-1 Group M, those encoded by Group O have not acquired the capacity to counteract tetherin. The defects map to the transmembrane domain and the membrane-proximal hinge region of the first alpha helix of the cytoplasmic tail; both are respectively defective for tetherin binding and trans-Golgi network-associated subcellular localization. As the panel of Vpu’s targets is increasing, we have collaborated with Paul Lehner’s group to identify new cellular substrates of Vpu. The glutamine transporter, SNAT-1, was identified by proteomic screening (SILAC). SNAT-1 is downregulated and degraded in HIV-1 infected CD4+ T cells. We are currently investigating the effects of Vpu-mediated SNAT-1 degradation and glutamine limitation on virus growth and cell proliferation/survival in primary CD4+ infected T cells. In parallel, we have investigated the molecular mechanism by which Vpu achieves SNAT-1 depletion.
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Chang, Jennifer Lynn. "Characterization of HIV-1 Rev mutants." Wright State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=wright1363271761.
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Wright, Alison Laing. "IGA MEDIATED DEFENSES AGAINST HIV-1." Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1201290332.
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Chinnadurai, Raghavan. "HIV-1 resistance to fusion inhibitors." [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-58600.
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Hermankova, Monika. "HIV-1 persistence under antiretroviral therapy." Available to US Hopkins community, 2002. http://wwwlib.umi.com/dissertations/dlnow/3080676.
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