Tesi sul tema "HIV Viruses"
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1
Wang, Yuan Min. "In vivo and in vitro dynamics of HIV-1 in patients with and without antiretroviral treatment". Thesis, The University of Sydney, 2002. https://hdl.handle.net/2123/27848.
Testo completoAbstract (sommario):
Highly active antiretroviral therapy (HAART) successfully reduces plasma levels of HIV-1 RNA and improves the quality of life for HIV-infected patients. However, these clinical benefits may be limited by the emergence of multiple drug- and cross drug resistance in HIV-1, and also by the concealment of these viral variants in other sanctuary sites such as
tissues, brain, lung and other blood cell types. Furthermore, the persistence of HIV reservoirs, including latently infected resting CD4 cells, brain, lymph tissue, bone marrow and genital tract, have posed a challenge to the long—term control or eradication of HIV infected patients received HAART. To determine the effect of HAART on the distribution
of viral variants, drug resistance variants, co-receptor surface expression and co—receptormediated viral entry in treated and untreated patients, we have carried out a detailed longitudinal and a comparative study on 6 seroconverters receiving HAART, in addition to 6 antiretroviral naive patients, and four patients receiving structured treatment interruption (STI). All treated patients were followed for 26 to 36 months from the initiation of HAART. In this study we have compared the interrupted and non-interrupted HAART patients to analyze the overall molecular, biological and cellular receptor dynamics over time, and highlight the advantages and disadvantages of the two therapies.
2
Burnside, Helen C. "Evaluation of Montana's HIV Prevention Social Marketing Campaign a descriptive study /". CONNECT TO THIS TITLE ONLINE, 2006. http://etd.lib.umt.edu/theses/available/etd-12042006-150921/.
Testo completo
3
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.
Testo completoAbstract (sommario):
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.
4
Razali, Karina National Centre in HIV Epidemiology & Clinical Research Faculty of Medicine UNSW. "Estimates and projections of HIV and Hepatitis C virus in Australia and the Asia-Pacific region". Publisher:University of New South Wales. National Centre in HIV Epidemiology & Clinical Research, 2008. http://handle.unsw.edu.au/1959.4/41095.
Testo completoAbstract (sommario):
The use of mathematical models in studying disease epidemics can be diverse, from the focused study of the role of a single determinant of the epidemic, or to the overall estimation of morbidity and mortality. In using simple deterministic models, a balance is struck between biological and social complexities, and the high data input demands of mathematical models. This thesis aims to apply the use of deterministic mathematical models to the studies of HIV and hepatitis C epidemiology in the Asia-Pacific region. In Australia, about 85% of reported HIV cases are among homosexual men. Casual homosexual partnerships made up 40% of incident HIV cases in 1995 increasing to 65% in 2004. In the state of New South Wales, it was estimated that over 7,500 people were living with HIV/AIDS in 2005, increasing to over 10,000 by 2016 with existing levels of intervention. Intervention measures were estimated to have prevented some 44,500 cases, the majority being among injecting drug users through the Needle and Syringe Programmes. Models for the HIV epidemics in developing countries were also developed incorporating multiple routes of HIV transmission. For Papua New Guinea, it was estimated 64,000 people were living with HIV/AIDS in 2005, rising to over 500,000 by 2025 with current levels of intervention. High levels of interventions, in particular increased condom use, will be required to achieve a stabilisation or reduction in HIV prevalence. In East Timor, the HIV epidemic is still in the early stages with 138 people estimated to be living with HIV/AIDS, rising to 5,000 by 2025 with minimal intervention. For HCV, models of the epidemic in Australia showed HCV incidence peaking in 1999, followed by a decline reaching 9,700 incident cases in 2005. Of 197,000 estimated chronic HCV cases in 2005, 58% had stage F 0/1 liver disease, 15% F 2/3 liver disease, and 2% HCV-related cirrhosis. Models estimated 210 and 105 people developed HCV-related liver failure and hepatocellular carcinoma, respectively. Comparisons of modelled HCV long-term sequelae projections with linkage data showed relatively good agreement, despite discrepancies in liver-related deaths. To decrease the number of chronic HCV, at least a tripling of treatment coverage would be required. These models provide estimates of the current levels of epidemics as well as projections of future scenarios under different intervention strategies, which have an important role in the planning of strategies, as well as assessment of previous epidemic conditions.
5
Lau, Katherine Aik Hee. "Biology and molecular biology of new HIV-1 recombinant forms from Malaysia". Connect to full text, 2008. http://hdl.handle.net/2123/4129.
Testo completoAbstract (sommario):
Thesis (Ph. D.)--University of Sydney, 2009.Title from title screen (viewed 31 March 2009). Submitted in fulfilment of the of the requirements for the degree of Doctor of Philosophy to the Discipline of Medicine, Faculty of Medicine. Degree awarded 2009; thesis submitted 2008. Includes bibliographical references. Also available in print form.
6
Hutchinson, Angela Blair. "A health technology assessment of HIV counseling and testing technologies evidence of effectiveness, cost-effectiveness and the consumer perspective /". Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-06072004-131203/unrestricted/hutchinson%5Fangela%5Fb%5F200405%5Fphd.pdf.
Testo completo
7
Juarez, Molina Claudia Ivette. "Population-specific HLA impact in immune control of HIV in Mexico and non-Mexican HIV infected cohorts". Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:2a6242d2-91bf-4029-9067-a922cbf1d8e4.
Testo completoAbstract (sommario):
HIV-1 persists to be a major health problem worldwide. A prophylactic or therapeutic vaccine offers the best hope to restrain the HIV-1 epidemic, however a consistent correlate of immune protection is yet to be found. HLA class I expression and their restricting HIV-1 specific CD8+ T cell responses have been shown to play a vital role in the control of HIV-1 infection. The interactions between HIV-1 and CD8+ T cell responses are complex and the mechanisms involved in the success or failure to control viraemia remain uncertain. Thus, the aim of these studies was to help define what CD8+ T cell responses a vaccine needs to induce to achieve durable immune control of HIV-1 infection. Focusing initially on HLA-B*35, an allele that has consistently been associated with rapid HIV-1 disease progression in the context of B clade infection, this study shows substantial differences in markers of HIV-1 disease outcome associated with different HLA-B*35 subtypes. Preliminary data suggest that effective targeting of a single epitope in Gag may be associated with HLA-B*35 mediated control of HIV-1 disease progression. Increased breadth of the Gag- specific CD8+ T cell responses is found to be associated with decreasing viral loads. These data therefore support the Gag hypothesis, and suggest that targeting of certain regions of the HIV-1 genome may have a positive effect in disease outcome, even for individuals carrying “detrimental” alleles. The extensive diversity of the HIV-1 genome and rapid viral adaptation are the main chal- lenges to vaccine design. Previous studies have suggested that effective CD8+ T cell responses drive selection of escape mutations that reduce viral replication capacity (VRC). There is also evidence that certain escape mutations can be transmitted from one host to another allow- ing for its accumulation in a population. The second study looked at the impact of HLA driven evolution of HIV-1 in VRC at a population level. This study compared two ART-naïve HIV-1 B clade infected cohorts, in Mexico and Barbados, in which protective HLA alleles (HLA- B*27/57/58:01/81:01) are expressed at 10% and 35% respectively, to analyze differences in VRC at a population level. Viral loads (VL) were found to be significantly higher in Mexico compared to Barbados and median CD4+ T cell counts significantly lower. Analysis of VRC in a subset of subjects in each cohort matched by CD4+ T cell counts between 300-500 cells/μl revealed that VL and VRC was significantly higher in the Mexican subset. This VRC difference was associated with accumulations in Barbados of eight previously described Gag escape mutation where fitness cost has previously been implicated. Accumulation remained significant in mismatched subjects. These data suggest that VLs and disease progression rates may differ between distinct populations as a result of the frequency of protective alleles in the respective populations, and that CD4+ T cell count-based guidelines to initiate antiretroviral therapy (ART) may need to be modified accordingly, to optimize the effectiveness of treatment-for-prevention strategies and reduce HIV-1 transmission rates to the absolute minimum. The final project aimed to improve the HIV-1 replication fitness assays currently used in the context of C clade infection. In order to achieve this, we attempted to design a clade C infectious molecular clone for the testing of gal-pol gene regions. However, the clones produced were not replication competent. Sequence analysis showed a large quantity of stop codons, most located within env which may explain the lack of infectivity. Chapter 5 describes the methodology used in the construction of the clade C isolate and suggests future work. Although we were unsuccessful in producing a replication competent virus, the construction of a C clade backbone which replicates efficiently remain an aim due to its importance for research directed to the analysis of genetic determinants of C clade virus. Data presented in this thesis suggest that vaccine-induced immune responses should aim to focus on vulnerable regions of the virus. These are conserved regions that can not escape without a high fitness cost and with a complex and difficult selection of compensatory mutations. Although much work remains to be done to achieve an effective CD8+ T cell based vaccine, hope remains that the induction of HIV control may be possible.
8
Maison, Barbara. "A content analysis of the New York times' coverage of HIV/AIDS in Africa from January 2000 to December 2007". Muncie, Ind. : Ball State University, 2009. http://cardinalscholar.bsu.edu/658.
Testo completo
9
Omune, Duncan Otieno. "Synthetic analogs of equisetin as potential HIV-1 integrase inhibitors". Diss., Online access via UMI:, 2004. http://wwwlib.umi.com/dissertations/fullcit/3150487.
Testo completo
10
Costiniuk, Cecilia T. "Oncolytic Viruses as a Potential Approach to Eliminate the HIV Reservoir". Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/23933.
Testo completoAbstract (sommario):
Similar to cancer cells, HIV-infected cells differ from HIV-uninfected cells in that they have altered interferon signaling pathways, the apparent reason for the selectivity of certain oncolytic viruses (OVs). Therefore, it was hypothesized that use of an OV, such as recombinant Maraba virus (MG1), may be a potential approach to eliminate latently-infected cells constituting the HIV reservoir while sparing HIV-uninfected cells. This was studied in U1, ACH-2, OM-10 and J1.1 cells and their respective HIV-uninfected parent cell lines in addition to CD4+CD25-HLADR- cells from HIV-infected individuals on effective antiretroviral therapy. Although MG1 infected and killed latently HIV-infected U1 cells to a greater degree than the HIV-uninfected parent U937 cells, this was not observed in the other HIV-infected cell lines and their respective parent cell lines. Furthermore, results from primary cells suggest that MG1 alone does not appear to eliminate cells which comprise the major HIV reservoir. Challenges of studying the HIV reservoir and priorities for future studies examining the use of OVs as a potential strategy to eliminate the HIV reservoir are discussed.
11
Exline, Colin Michael Stoltzfus C. Martin. "The positive regulation of HIV-1 Vif mRNA splicing is required for efficient virus replication". [Iowa City, Iowa] : University of Iowa, 2009. http://ir.uiowa.edu/etd/356.
Testo completo
12
Pace, Craig Stuart. "The influence of APOBEC3G and deoxythymidylate kinase genetic diversity on HIV-1 hypermutation and response to treatment". Thesis, Pace, Craig Stuart (2006) The influence of APOBEC3G and deoxythymidylate kinase genetic diversity on HIV-1 hypermutation and response to treatment. PhD thesis, Murdoch University, 2006. https://researchrepository.murdoch.edu.au/id/eprint/242/.
Testo completoAbstract (sommario):
This thesis addresses two important topics in HIV-1 medicine; (i) the clinical relevance of pre-treatment G-A hypermutation and the contribution of host and viral genetics to its development and; (ii) the influence of genetic variation in host enzymes responsible for antiretroviral drug metabolism on response to therapy. These themes are outlined below.
HIV-1 Hypermutation
At present, limited data exists regarding the relative roles of host encoded cytidine deaminases APOBEC3G and APOBEC3F in promoting G-A hypermutation of HIV-1 proviral DNA in vivo, nor the clinical relevance of hypermutation or the influence of genetic diversity of the APOBEC3G locus and of the viral encoded vif protein that counteracts the action of APOBEC3G. The analyses contained within this thesis demonstrate that within the WA HIV cohort, clinically relevant hypermutation is restricted to a minority of individuals and is mediated predominantly by APOBEC3G. In this study, the presence of HIV-1 hypermutation had a substantially greater effect on plasma viremia than other known host antiviral factors such as CCR5D32 or specific HLA-B alleles. Furthermore, the considerable genetic diversity of the vif gene is likely to make a greater contribution to the development of hypermutation than the limited genetic diversity of the APOBEC3G gene in Caucasians. These data indicate that G-A hypermutation is a clinically relevant phenomenon and may provide a fresh perspective to the area of HIV/AIDS therapies.
Genetic Determinant of HIV-1 Treatment Response
Thymidine kinase 2 (TK2) and thymidylate kinase (dTMPK) are rate limiting enzymes for the metabolism of the antiretrovirals d4T and AZT, respectively, and are thus central to the antiviral efficacy and toxicity of these agents. However, the genetic diversity of TK2 and dTMPK and their influence on toxicities associated with their use is largely unknown. The results discussed in this thesis indicate that in contrast to the highly conserved TK2 locus, the dTMPK locus of Caucasian individuals, including regulatory regions potentially influencing transcription and translation, is considerably polymorphic and organised into five common haplotypes. The results regarding the contribution of dTMPK genetic variation to toxicities associated with AZT therapy are encouraging. A common dTMPK haplotype had significant, albeit modest, effect on haematological parameters (haemoglobin and mean corpuscular volume) in HIV-infected patients, although no AZT-specific treatment effect was observed in this relatively haematologically stable cohort. In addition, another common dTMPK haplotype provided significant protection against AZT-induced adipocyte mtDNA depletion in a pilot study of AZT- and d4T-treated individuals. The dTMPK haplotypes characterised in this thesis should facilitate further studies regarding dTMPK genetic variation in HIV-1 infection and response to treatment, which are warranted from the clinical results presented herein.
13
Pace, Craig Stuart. "The influence of APOBEC3G and deoxythymidylate kinase genetic diversity on HIV-1 hypermutation and response to treatment". Pace, Craig Stuart (2006) The influence of APOBEC3G and deoxythymidylate kinase genetic diversity on HIV-1 hypermutation and response to treatment. PhD thesis, Murdoch University, 2006. http://researchrepository.murdoch.edu.au/242/.
Testo completoAbstract (sommario):
This thesis addresses two important topics in HIV-1 medicine; (i) the clinical relevance of pre-treatment G-A hypermutation and the contribution of host and viral genetics to its development and; (ii) the influence of genetic variation in host enzymes responsible for antiretroviral drug metabolism on response to therapy. These themes are outlined below.
HIV-1 Hypermutation
At present, limited data exists regarding the relative roles of host encoded cytidine deaminases APOBEC3G and APOBEC3F in promoting G-A hypermutation of HIV-1 proviral DNA in vivo, nor the clinical relevance of hypermutation or the influence of genetic diversity of the APOBEC3G locus and of the viral encoded vif protein that counteracts the action of APOBEC3G. The analyses contained within this thesis demonstrate that within the WA HIV cohort, clinically relevant hypermutation is restricted to a minority of individuals and is mediated predominantly by APOBEC3G. In this study, the presence of HIV-1 hypermutation had a substantially greater effect on plasma viremia than other known host antiviral factors such as CCR5D32 or specific HLA-B alleles. Furthermore, the considerable genetic diversity of the vif gene is likely to make a greater contribution to the development of hypermutation than the limited genetic diversity of the APOBEC3G gene in Caucasians. These data indicate that G-A hypermutation is a clinically relevant phenomenon and may provide a fresh perspective to the area of HIV/AIDS therapies.
Genetic Determinant of HIV-1 Treatment Response
Thymidine kinase 2 (TK2) and thymidylate kinase (dTMPK) are rate limiting enzymes for the metabolism of the antiretrovirals d4T and AZT, respectively, and are thus central to the antiviral efficacy and toxicity of these agents. However, the genetic diversity of TK2 and dTMPK and their influence on toxicities associated with their use is largely unknown. The results discussed in this thesis indicate that in contrast to the highly conserved TK2 locus, the dTMPK locus of Caucasian individuals, including regulatory regions potentially influencing transcription and translation, is considerably polymorphic and organised into five common haplotypes. The results regarding the contribution of dTMPK genetic variation to toxicities associated with AZT therapy are encouraging. A common dTMPK haplotype had significant, albeit modest, effect on haematological parameters (haemoglobin and mean corpuscular volume) in HIV-infected patients, although no AZT-specific treatment effect was observed in this relatively haematologically stable cohort. In addition, another common dTMPK haplotype provided significant protection against AZT-induced adipocyte mtDNA depletion in a pilot study of AZT- and d4T-treated individuals. The dTMPK haplotypes characterised in this thesis should facilitate further studies regarding dTMPK genetic variation in HIV-1 infection and response to treatment, which are warranted from the clinical results presented herein.
14
Kok, Tuckweng. "Early events in the replication cycle of human immunodeficiency virus /". Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phk79.pdf.
Testo completoAbstract (sommario):
Thesis (Ph. D.)--University of Adelaide, Dept. of Microbiology & Immunology, 1998.Copy of author's previously published article on back end-paper. Includes bibliographical references (leaves 105-158).
15
Grzybowski, Brad. "A pseudotyped viral vector : hPIV3-HIV-1". Thesis, Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/20932.
Testo completo
16
Njiba, Jessica Tshiosha. "Access to HIV treatment for refugees : case study of South Africa and Uganda". Thesis, University of the Western Cape, 2015. http://hdl.handle.net/11394/5296.
Testo completo
17
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.
Testo completo
18
Walker, Polly Rose. "Evolution and infectivity of HIV-1 subtype C viruses". Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.442985.
Testo completo
19
Sekgota, Khethobole Cassius. "Design, development and evaluation of novel lead compounds as HIV-1 enzyme inhibitors". Thesis, Rhodes University, 2015. http://hdl.handle.net/10962/d1017926.
Testo completoAbstract (sommario):
This project has been concerned with the application of the Baylis-Hillman methodology to the synthesis of medicinally important diketo acid analogues (cinnamate ester-AZT conjugates and 3-hydroxy ester-AZT conjugates) as dual-action HIV-1 IN/RT inhibitors; and on exploratory studies in the preparation of 3-(amidomethyl)-(1H)-2-quinolones as PR inhibitors; and (1H)-2- quinolone-AZT conjugates as dual action IN/RT inhibitors. A series of Baylis-Hillman adducts has been prepared, typically in moderate to excellent yield, by reacting 2-nitrobenzaldehyde with methyl acrylate, ethyl acrylate and methyl vinyl ketone in the presence of 1,4- diazabicyclo[2.2.2]octane (DABCO). Subsequently, various transformations that include conjugate addition of primary and secondary amines to the α,ß-unsaturated moiety to obtain 2- (aminomethyl)-3-hydroxy-3-(2-nitrophenyl)propanoate derivatives, effective SN2´ substitution of the BH ß-hydroxy by a Vilsmeier-Haack in situ-generated chloride to afford Baylis-Hillman allyl chlorides, iron in acetic acid-catalyzed cyclisation to 3-acetoxymethyl-(1H)-2-quinolone derivatives were achieved. Thus, using the Baylis-Hillman methodology, two nuanced classes of diketo acid analogues were constructed. These involved conjugating appropriate propargylamine derivatives with AZT using the „click‟ reaction. In an exploratory study, the quinolone derivative, precisely 3-acetoxymethyl- (1H)-quinol-2-one, was transformed into 3-hydroxymethyl-(1H)-quinol-2-one using potassium carbonate in a mixture of methanol and water (1:1). Following successful hydrolysis, the resulting alcohol was transformed to the corresponding chloride, 3-chloromethyl-(1H)-quinol-2- one, using thionyl chloride. Subsequent nucleophilic substitution afforded 3-(aminomethyl)- (1H)-2-quinolone derivatives which were subsequently transformed to 3-(amidomethyl)-(1H)-2- quinolones; and 3-[(propargylamino)-methyl]-(1H)-quinol-2-one as precursors to quinolone- AZT derivatives. All compounds were characterized by NMR, IR, and where appropriate, high resolution MS
20
James, Katherine Louise. "Viral genetics of HIV-2 infection". Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:68ba022d-62e4-4cb1-8032-085ea5240b98.
Testo completoAbstract (sommario):
HIV-2 is a contemporary human retrovirus with the majority of infections localised to West Africa. Both HIV-1 and HIV-2 are able to cause AIDS; however, in contrast to HIV-1 infection, a common outcome following HIV-2 infection (∼ 37% of patients in this study cohort) is long-term non-progression (LTNP), where patients remain aviraemic and asymptomatic in the absence of treatment, often for decades. HIV-1 and HIV-2 both arose following zoonotic transmission of SIVs from non-human primates at around the beginning of the 20th century and when patients develop AIDS caused by HIV-2 infection, it is clinically indistinguishable from AIDS following HIV-1 infection. Whilst the estimated number of HIV-2 infections remains small in the context of the global HIV pandemic (HIV-2 ∼ 2 million, HIV-1 group M ∼75 million), the differences in pathogenicity between these two viruses has been a source of great interest, particularly the features of LTNPs that allow control of viral replication in the absence of anti-retroviral treatment. The studies described in this thesis were carried out using samples collected from a well-characterised longitudinal community cohort in Caió, Guinea-Bissau. Chapter 3 of this thesis presents an investigation into the variation and evolution present in the HIV-2 specific accessory gene vpx. The data showed significantly increased signals of positive selection pressure in vpx in viraemic when compared to non-viraemic patients and also allowed the identification of novel variations at high frequencies (up to 22%) in this cohort that were previously un-described. Chapters 4 and 5 present a novel application of shotgun RNA sequencing (RNA- Seq) to HIV ex vitro and ex vivo samples. Chapter 4 demonstrates the divergence seen in a cultured viral isolate at the level of the whole genome, in the absence of many of the biases typically involved in sequencing of RNA viruses. Chapter 5 further extends this method to show the applicability of using RNA-Seq on primary patient HIV samples for the first time. Analysis of diversity estimates over the whole genome in the context of a low bias sequencing method show a high level of diversity in HIV-2 pol and low diversity in vpx. The aim of this work was to combine traditional and novel sequencing methods to facilitate assessment of the variation and evolution acting on vpx and to generate an accurate picture of the genetic diversity over the whole genome of HIV-2.
21
Jowett, Jeremy Bryan Mark. "Properties of recombinant HIV and SIV antigens". Thesis, University of Oxford, 1992. http://ora.ox.ac.uk/objects/uuid:5de3119b-4aa1-469a-80b6-f1f28dff4f5c.
Testo completoAbstract (sommario):
When expressed in Spodoptera frugiperda cells using recombinant baculoviruses, the HIV - 1 gag gene product, p55, self assembles to form immature HIV core like particles that are secreted into the culture medium. Using this system, the gag open reading frame was progressively truncated from the carboxy terminus, and each deleted Gag protein examined for its ability to produce core like particles. Deletions that removed the distal region of the Gag nucleocapsid domain, including both Cys - His motifs thought to function as RNA capture signals, did not disrupt particle formation. Analysis of the truncation mutants by north - western blot with a radiolabelled HIV - 1 RNA encapsidation signal, confirmed that only precursors with the Cys - His motif present were able to bind the probe. It was concluded that HIV - 1 Gag particle formation per se does not require RNA encapsidation. This finding clarifies uncertainties proposed previously regarding the role of RNA encapsidation in particle assembly. Further deletion mutants led to the delineation of the carboxy terminal boundary of a Gag assembly domain. Properties of the SIV env encoded TM glycoprotein were also explored. Previous reports have found that the cytoplasmic tail of this membrane spanning protein was preferentially deleted in vivo when SIV was grown in a variety of cultured human cells. However, when propagated in cells of simian origin, the TM glycoprotein cytoplasmic tail was retained. Analysis of the function of this domain was addressed by expression of both the truncated and the full length proteins in insect cells using recombinant baculoviruses, coupled with a study of their biochemical characteristics. A role for the cytoplasmic tail was identified in the post - translational modification and localization of the glycoprotein. The use of the Gag particles in designing vaccines was investigated. Acting as non - infectious carriers of immunogenic antigens, the particles represent a safe and efficient means for presentation of epitopes for eliciting a protective immune response. Two possible approaches for loading the particles with foreign antigen were examined. In the first, the deleted portion of Gag was replaced with a sequence encoding the foreign antigen. The second method involved co - expression of Gag with another recombinant virus that expressed a foreign antigen on the surface of the cell. Both methods were found to be feasible, although limitations were identified when addition of the fusion protein promoted excess degradation of the Gag precursor.
22
Jacobs, Graeme Brendon. "Investigation of the molecular epidemiology of HIV-1 in Khayelitsha, Cape Town, using serotyping and genotyping techniques". Thesis, Link to the online version, 2005. http://hdl.handle.net/10019/1056.
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23
Davis, Adam James. "Transcriptional analysis of human immunodeficiency virus type 1 infection following cell-to-cell transmission /". Title page, contents and abstract only, 1997. http://web4.library.adelaide.edu.au/theses/09PH/09phd2609.pdf.
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24
Clark, Nigel John. "The control of HIV-1 envelope expression by Rev". Thesis, University of Reading, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336085.
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25
Williams, Claire Amy. "The role of RNA helicases in HIV-1 replication". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610047.
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26
Turville, Stuart Grant. "HIV attachment, trafficking and transmission in human dendritic cells". Thesis, The University of Sydney, 2003. https://hdl.handle.net/2123/28001.
Testo completoAbstract (sommario):
Dendritic cells (DC) provide a bridge between the innate and acquired immune system. HIV exploits the complex pathways of microbial antigen uptake and transport by these cells for initial entry and dissemination. Over the past few years the binding of gp120 to the C type lectin DC-SIGN on transfected cells and dendritic cells has been investigated and proposed as the major receptor for HIV binding on (all) DCs. However in this thesis the C type lectin receptors (CLRs), langerin, uniquely expressed on Langerhans cells (LC), and mannose receptor (MR) shown to be expressed on dermal DC subsets were also demonstrated to bind HIV gp120 through its mannose saccharides in addition to
DC-SIGN.
27
Sharrocks, Katherine Elizabeth. "Host cell factors facilitating HIV-1 integration". Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670169.
Testo completo
28
Hutchinson, Angela Blair. "A health technology assessment of HIV counseling and testing technologies". Diss., Georgia Institute of Technology, 2004. http://hdl.handle.net/1853/8077.
Testo completo
29
Helbert, Matthew Reginald. "HIV infection in sub-populations of CD4+ lymphocytes defined by CD45". Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261804.
Testo completo
30
Yao, Felix Caspar. "Investigation on the risk of viral infection in musculoskeletal grafts". University of Western Australia. School of Surgery, 2010. http://theses.library.uwa.edu.au/adt-WU2010.0068.
Testo completoAbstract (sommario):
[Truncated abstract] Around 50,000 hip and knee replacements are performed every year in Australia and this number has been increasing by around 13% annually since 1998 (Transplantation Society 2006). The incidence and number of revision surgery has increased by a similar proportion. Autogenous bone or allograft is still the gold standard grafting material and is currently used in a variety of reconstructive surgical procedures. The use of any allograft material carries with it the risk of transfer of disease from donor to recipient. These tissues can transmit the same viral and bacterial infections as blood, and the products of a single donation may be transplanted to several recipients. In contrast to blood, musculoskeletal tissues may come from surgical and cadaveric donation. Overall, the prevention of infection relies on the maintenance of rigid protocols for procurement, donor and allograft testing, secondary sterilisation, and the adherence to internal safety standards within the tissue banks. This thesis aims to determine the risk of viral infection among musculoskeletal tissue donors in Australia. We retrieved and analysed data retrospectively from three large tissue banks in Australia (Perth, Queensland, Victoria). This includes 12,415 musculoskeletal tissue donors, 10,937 of which are surgical donors and 1,478 of which are deceased donors, for the period of 1993 -2004. This data was analysed to determine the prevalence and incidence of viral infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T-lymphotropic virus (HTLV) in musculoskeletal allografts. The results indicate that the risk of viral infection from musculoskeletal tissue transplantation in Australia is low. ... The results indicate that the overall prevalence of screened transfusion-transmitted viral infections did not vary significantly for musculoskeletal donors over the study period, despite falling in the general population and first-time blood donors. In tissue donors, HIV incidence significantly decreased over time, and HBV decreased significantly during 1999-2001; however, there was an apparent increase in the estimated incidence of HCV in 2002-2004 compared with earlier years. Furthermore the residual risk estimate of HIV in the period 2002-2004 has declined 5-fold compared to estimates in the period 1993-1995. This is perhaps due to greater awareness of high risk behaviours among donors, improvement in donor recruitment and an overall decrease in infection levels in the general population. Musculoskeletal tissue is second only to blood as the most frequent transplanted human tissue. Viral infection is a potential complication of tissue transplantation. In this thesis the rates of HIV, HBV, HCV and HTV infection in musculoskeletal donors in Australia were identified and then compared with results in published data from Canada, Scotland and the United States. The study also compared that result with first-time blood donors because they have satisfied similar donor selection criteria (Galea et al. 2006). The results indicate that prevalence and incidence estimates for viral infection in Australian tissue donors are higher than those in blood donors. This was also reported in studies from other countries. Accordingly, it is crucial that viral prevalence and incidence be monitored to evaluate the safety of tissue supply and to improve donor selection processes.
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Smith, Jacqueline D. "Analysis of HIV-1 specific antibodies induced by Ugandan viruses or virus encoded peptides". Thesis, Open University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413809.
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Tasca, Karen Ingrid [UNESP]. "Parâmetros imunovirológicos em pacientes infectados pelo HIV, tratados ou não com antirretrovirais". Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/89948.
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Universidade Estadual Paulista (UNESP)
O Brasil é um dos países mais afetados pelo HIV, com notificação de 608.230 casos acumulados de 1980 até junho de 2011, com a maior concentração na região Sudeste. Sabe-se que, entre muitos outros fatores a progressão para aids sofre influência de variáveis metabólicas, virológicas e imunológicas. Além disso, persistente ativação imune e contínuo estímulo inflamatório, mesmo durante a terapia antirretroviral (TARV) ou ausência de sintomatologia, podem levar ao desequilíbrio de várias citocinas e influenciar, potencialmente, a progressão da própria doença ou outras comorbidades, que são determinantes para aumentar a morbidade e mortalidade, associadas ou não à aids. Foram estudados 80 voluntários atendidos no Serviço de Ambulatórios Especializados e Hospital Dia “Domingos Alves Meira”, FMB/UNESP e no Hemocentro de Botucatu, divididos em quatro grupos: 20 pacientes com infecção pelo HIV, virgens de tratamento (G1); 20 pacientes em uso de TARV com carga viral (CV) detectável (G2); 24 pacientes em uso de TARV com CV indetectável (G3); 16 indivíduos saudáveis, grupo controle (GC). O objetivo do estudo foi avaliar parâmetros imunovirológicos (contagem de linfócitos T CD4+, T CD8+ e dosagem da CV plasmática do HIV) de pacientes infectados pelo HIV, correlacionando citocinas séricas inflamatórias (IL-6, IL-17, TNF- e IFN-) e antinflamatória (IL-10) pelo método de ELISA, tempo de infecção, uso de TARV e outros exames laboratoriais (hemograma, perfil lipídico, glicemia, enzimas hepáticas, DHL, creatinina e PCR). As comparações das variáveis numéricas em relação aos grupos foram feitas utilizando o teste de Mann-Whitney, Kruskal-Wallis, seguido de teste de Dunn e análise da variância ANOVA, seguido de Tukey...
Brazil is one of the most affected countries by HIV, reporting 608,230 cases that have accumulated from 1980 to June 2011 with the largest concentration in the south-east. It is known that, among many other factors, progression to AIDS is influenced by metabolic, virological and immunological variables. Moreover, persistent immune activation and continuous inflammatory stimulus, even during antiretroviral therapy (ART), or the absence of symptomatology may lead to the instability of various cytokines and potentially influence the progression of the disease itself or other comorbidities that are determinant to increase morbidity and mortality in association with AIDS or not. Eighty volunteers were assisted and studied in the Specialized Outpatient Service and Day Hospital “Domingos Alves Meira” at the Botucatu School of Medicine (FMB) - UNESP and at the Hemocenter of Botucatu. They were divided into four groups: 20 HIV-infected patients who had never been treated (G1); 20 patients using ART with a detectable viral load (VL) (G2); 24 patients using ART with undetectable VL (G3); 16 healthy individuals, control group (CG). The study aimed at evaluating immunovirological parameters (T CD4+, T CD8+ lymphocyte count and HIV plasma VL quantification) of HIV-infected patients and correlate them with inflammatory (IL-6, IL-17, TNF- and IFN-) and anti-inflammatory (IL-10) serum cytokines by the ELISA method, time of infection, ART use and other laboratory tests (hemogram, lipid profile, glycemia, liver enzymes, LDH, creatinine and CRP). Comparison of numeric variables in relation to the groups were performed by using the Mann-Whitney, Kruskal-Wallis test followed by Dunn’s test, analysis of variance ANOVA and Tukey’s test. Associations were made between variables and the study groups by analyzing contingency tables with the application of the... (Complete abstract click electronic access below)
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Rhodes, Terence D. "High frequencies of HIV-1 recombination and the evolutionary potential of a hybrid retrovirus". Morgantown, W. Va. : [West Virginia University Libraries], 2006. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=4563.
Testo completoAbstract (sommario):
Thesis (Ph. D.)--West Virginia University, 2006.Title from document title page. Document formatted into pages; contains vi, 143 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.
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Enriquez-Enriquez, Carlos. "Detection and survival of selected viruses in water". Diss., The University of Arizona, 1994. http://hdl.handle.net/10150/186948.
Testo completoAbstract (sommario):
Nucleic acid hybridization (gene probe) and polymerase chain reaction (PCR) techniques have been used to detect viral nucleic acid in water. However, gene probe and PCR may not distinguish between infectious and noninfectious viruses. This study evaluated the ability of gene probe to detect viable poliovirus 1 (polio 1), from sterile and nonsterile groundwater, and the ability of PCR to detect infectious human immunodeficiency virus (HIV-1) from tap and wastewater. The plaque forming (BGM cells), and the tissue culture infectious dose fifty (TCID₅₀) (PLC/PRF/5 cells) procedures were used to detect infectious polio 1 and HIV-1, respectively. Detection of polio 1 by gene probe and cell culture was similar in nonsterile water and in filter sterilized water, but not in autoclaved water. These results suggest that in some natural waters, detection of polio 1 by gene probe may correlate to detection by cell culture procedures. Although detection of infectious HIV-1 by cell culture decreased gradually, until no virus could be found, detection by PCR remained positive throughout the study. Therefore, it was concluded that the use of PCR to assess the risk associated to the presence of HIV-1 in polluted waters, may not be adequate. The enteric adenovirus types 40 (Ead 40) and 41 (Ead 41) are considered the second most important cause of viral gastroenteritis in children, but their role as waterborne pathogens is uncertain. This study compared the survival of Ead 40 and Ead 41 with polio 1, and hepatitis A virus (HAV) in different types of water. The Enteric adenoviruses survived longer in tap and sea water than either polio 1 or HAV, but only slightly better in wastewater. These results suggest that the enteric adenoviruses may survive for prolonged periods in water, representing a potential route of transmission. This study evaluated also the concentration of Ead 40 by the filter adsorption-elution method. With negatively-charged filters, recovery efficiencies of 22, 36, and 38% were obtained from secondary sewage, tap and sea water, respectively. Using electropositive filters, Ead 40 was recovered from tap water with an efficiency of 26.5%. These results show that Ead 40 can be concentrated, from water, with an efficiency comparable to that of other enteric viruses.
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McCarthy, Marilyn Rae. "Speaking the unspeakable : the themes, issues and concerns of seven HIV/AIDS educators in South Australia /". full text, 1993. https://www.library.health.sa.gov.au/Portals/0/speaking-the-unspeakable-the-themes-1993.pdf.
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Thesis (M. Ed.)--University of South Australia, 1993."Report of a thesis submitted for a masters in Education, Human Resource Studies August 1993"--Cover. Includes bibliographical references (leaf 178-188).
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Zhang, Haojie, e 張浩杰. "Functional study of the turn between helix h and i of HIV-1 reverse transcriptase thumb subdomain". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41508580.
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Wu, Hao, e 吴昊. "Identification of drug resistant mutations in HIV-1 latently infected patients under successful HAART and in CRF_BC variants selected invitro". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47149826.
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Lee, Natasha Chun Yi. "RNA interference to study host factors required for human immunodeficiency virus-1 replication". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610703.
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Zhang, Haojie. "Functional study of the turn between helix h and i of HIV-1 reverse transcriptase thumb subdomain". Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41508580.
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Leon, Jorge Esquiche. "Estudo histopatologico, imunoistoquimico e de hibridização ¿in situ¿ das glandulas submandibular e sublingual em pacientes autopsiados com aids em fase avançada". [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288420.
Testo completoAbstract (sommario):
Orientador: Pablo Agustin VargasTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Os objetivos do presente estudo foram descrever as características histopatológicas, immunoistoquímicas e de hibridização "in situ" (HIS) das lesões encontradas nas glândulas submandibular e sublingual de pacientes autopsiados com AIDS entre 1996 e 1999 no Serviço de Verificação de Óbitos da Capital (SVOC) - Faculdade de Medicina da Universidade de São Paulo (FMUSP). Dados referentes ao gênero, idade, contagem de células TCD4 e história clínica foram obtidos dos prontuários clínicos de 105 pacientes, destes 103 casos corresponderam às glândulas submandibulares e 92 casos às sublinguais. Todas as glândulas foram examinadas macroscopicamente e no estudo histopatológico utilizamos colorações de H&E, Gomori-Grocott; Ziehl-Neelsen e Mucicarmin. Análise imunoistoquímica foi realizada para detectar os agentes infecciosos (CMV, LMP-EBV, HSV-l, HSV-2, p24-HIV e BCG) e caracterizar as sialadenites (CD3, CD4, CD8, CD20 e CD68), já a HIS analizou a presença do VEB (EBER1/2). A média de idade dos pacientes e o nível de células TCD4 nos casos das glândulas submandibular e sublingual foi de 36,62 '+ ou ¿ ¿ 11,18 anos e 74,37 '+ ou ¿ ¿ 112,82 células/¿mu'L, e 35,93 '+ ou ¿ ¿ 0,2 anos e 78,75 '+ ou ¿ ¿ 118,98 células/¿mu'L, respectivamente. Foram considerados microscopicamente normais .51 (49,5%) casos da glândula submandibular e 54 (58,7%) casos da sublingual. As lesões infecciosas foram as mais freqüentes na glândula submandibular (n=35), seguida pela sialadenite crônica inespecífica em ambas as glândulas (n=25). Micobacteriose (11 e 07 casos nas glândulas submandibular e sublingual, respectivamente), citomegalovirose (14 e 02 casos nas glândulas submandibular e sublingual, respectivamente) e criptococose (03 e 04 casos nas glândulas submandibular e sublingual, respectivamente) foram freqüentemente detectadas. A análise imunoistoquímica mostrou que todos os casos em ambas as glândulas foram negativos para LMP-EBV, HSV-l e HSV-2, enquanto BCG mostrou intensa imunopositividade somente nos casos de micobacteriose com padrão macrofágico difuso (n=2). Dos 16 casos de citomegalovirose, apenas 06 casos (05 e 01 caso nas glândulas submandibular e sublingual, respectivamente) foram detectados pela imunoistoquímica. A proteína p24-HIV (02 e 01 caso nas glândulas submandibular e sublingual, respectivamente) e EBER1/2 (09 e 04 casos nas glândulas submandibular e sublingual, respectivamente), este último avaliado somente nos casos de sialadenités, foram expressas somente em escassos histiócitos e linfócitos, respectivamente, indicando que a participação destes vírus na etiopatogênese das sialadenites é pouco provável e precisa ser ainda melhor definida. As sialadenites crônicas inespecíficas foram principalmente compostas por linfócitos TCD8 (p=0,323); enquanto as sialadenites granulomatosas, as sialadenites macrofágicas difusas associada com micobacteriose e as sialadenites macrofágicas difusas inespecíficas apresentaram grande quantidade de macrófagos CD68+ (p=0,99) permeados por numerosos linfócitos TCD8, em ambas as glândulas. Além disso, um caso de linfoma não-Hodgkin difuso de grandes células B afetou ambas as glândulas. Estes resultados mostram que as glândulas submandibular e sublingual foram principalmente acometidas por lesões infecciosas disseminadas e sialadenite crônica inespecífica. Similarmente, as glândulas parótidas, num estudo previamente publicado por nossa equipe, foram acometidas por lesões infecciosas sistêmicas. Sendo assim, os clínicos devem estar atentos à ocorrência destas lesões em glândulas salivares maiores de pacientes com AIDS em fase avançada
Abstract: This study describes the histopathological, immunohistochemical (lHC), and in situ hybridization (ISH) features found in the submandibular (n=103) and sublingual (n=92) glands of autopsied patients who died with AIDS between 1996 and 1999 in the SVOC FMUSP (Medical School of São Paulo University). Sex, age, CD4 cell count, and clinical history were obtained from the clinical records of 105 patients, of them 103 cases corresponded to the submandibular glands and 92 cases to the sublingual glands. All glands were examined for macroscopical alterations and stained using H&E, Gomori-Grocott, Ziehl-Neelsen, and Mucicarmine. IHC analysis to detect infectious agents (CMV, LMP-EBV, HSV-l, HSV-2, HIV-p24, and BCG) and to characterize the sialadenitis (CD3, CD4, CD8, CD20, and CD68) was performed, while the ISH assessed the presence of EBV (EBERl/2). The mean age of the patients and CD4 cell count of the cases of the submandibular and sublingual glands were 36,62 '+ or ¿ ¿ 11,18 years and 74,37 '+ or ¿ ¿ 112,82 cells¿mu¿L POT .-1¿, and 35,93 '+ or ¿ ¿ 10,2 years and 78,75 '+ or ¿ ¿ 118,98 cells¿mu¿¿L POT .-1¿, respectively. There were no histological alterations in 51 (49,5%) and 54 (58,7%) cases of the submandibular and sublingual glands, respectively. The infection conditions were the most common in the submandibular gland (n=35), followed by chronic non-specific sialadenitis in both glands (n=25). Mycobacteriosis (11 and 07 cases of the submandibular and sublingual glands, respectively), cytomegalovirosis (14 and 02 cases of the submandibular and sublingual glands, respectively), and cryptococcosis (03 and 04 cases of the submandibular and sublingual glands, respectively) were found frequently. The IHC analysis did not show immunoreactivity for LMP-EBV, HSV-l, and HSV-2; while BCG displayed strong immunopositivity only in cases of chronic diffuse macrophagic infiltrate associated to mycobacteriosis (n=2). Six out of 16 cases of cytomegalovirosis (05 and 01 case of the submandibular and sublingual glands, respectively) were detected for IHC analysis only. The p24-HIV protein (02 and 01 case of the submandibular and sublingual glands, respectively) and EBERl/2 (09 and 04 cases of the submandibular and sublingual glands, respectively), this latter evaluated only in the sialadenitis cases, were expressed only in macrophages and lymphocytes, respectively, indicating that the participation of these viruses in the etiopathogenesis of the sialadenitis is still unc1ear. Chronic non-specific sialadenitis revealed CD8+ T-lymphocytes predominance (p=0,323), hile the granulomatous, diffuse macrophagic associated to mycobacteriosis, and chronic non-specific diffuse macrophagic sialadenitis showed great amount of CD68+ macrophages (p=0,99) surrounded by numerous CD8+ T-lymphocytes, in both glands. Moreover, one case of diffuse large B-celllymphoma affected both glands. These results indicate that both submandibular and sublingual glands were affected mainly by infectious diseases and chronic non-specific sialadenitis. Similarly, the parotid glands in a study previously published by our team, were mainly affected for systemic infectious diseases. Therefore, c1inicians should consider more carefully the occurrence of these lesions in major salivary glands of patients with advanced AIDS
Doutorado
Patologia
Doutor em Estomatopatologia
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Mlobeli, Regina. "HIV/AIDS Stigma: an investigation into the perspectives and expereinces of people living with HIV/AIDS". Thesis, University of the Western Cape, 2006. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_6069_1189595852.
Testo completoAbstract (sommario):
People's attitudes towards people living with HIV/AIDS remain a major community challenge. There is a need to generate a climate of understanding, compassion and dignity in which people living with HIV/AIDS (PLWHA) will be able to voluntarily disclose their status and receive the support and respect all people deserve. However, many people expereince discrimination because they have HIV/AIDS. In a certain area in Khayelitsha, a township in Cape Town, a young woman was killed after disclosing the HIV status after being raped by five men. While many previous studies have focused on the external stigma in the general population, there is a dearth of studies on stigma among PLWHA themselves and hence the aim of the present study was to investigate stigma attached to HIV/AIDS from the perspective of PLWHA.
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Munoz, Liliana Beatriz. "The interaction between the HIV-1 tat protein and PKR /". [St. Lucia, Qld], 2004.
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Li, Chun-bong. "Mechanisms of HIV-1 Tat induced immune response". Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31537169.
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Li, Chun-bong, e 李振邦. "Mechanisms of HIV-1 Tat induced immune response". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B31537169.
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McKnight, Aine Veronica. "Tropism and neutralization of human and simian immunodeficiency viruses". Thesis, Institute of Cancer Research (University Of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244796.
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Ranganath, Nischal. "Oncolytic Viruses as a Potential Approach to Eliminate Cells That Constitute the Latent HIV Reservoir". Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37355.
Testo completoAbstract (sommario):
HIV infection represents a major health and socioeconomic challenge worldwide. Despite significant advances in therapy, a cure for HIV continues to be elusive. The design of novel curative strategies will require targeting and elimination of cells that constitute the latent HIV-1 reservoir. However, such an approach is impeded by the inability to distinguish latently HIV-infected cells from uninfected cells.
The type-I interferon (IFN-I) response is an integral antiviral defense mechanism, but is impaired at multiple levels during productive HIV infection. Interestingly, similar global impairments in IFN-I signaling have been observed in various human cancers. This led to the development of IFN-sensitive oncolytic viruses, including the recombinant Vesicular Stomatitis Virus (VSV 51) and Maraba virus (MG1), as virotherapy designed to treat various cancers.
Based on this, it was hypothesized that IFN-I signaling is impaired in latently HIV-infected cells (as observed in productively infected cells) and that VSV 51 and MG1 may be able to exploit such intracellular defects to target and eliminate latently HIV-infected cells, while sparing healthy cells. First, using cell line models of HIV-1 latency, intracellular defects in IFN-I responses, including impaired IFN / production and expression of IFNAR1, MHC-I, ISG15, and PKR, were demonstrated to represent an important feature of latently HIV-infected cells. Consistent with this, the latently HIV-infected cell lines were observed to have a greater sensitivity to VSV 51 and MG1 infection, and MG1-mediated killing, than the HIV-uninfected parental cells.
Next, the ability of oncolytic viruses to kill latently HIV-infected human primary cells was demonstrated using an in vitro resting CD4+ T cell model of latency. Interestingly, while both VSV 51 and MG1 infection resulted in a significant reduction in inducible p24 expression, a dose-dependent decrease in integrated HIV-1 DNA was only observed following MG1 infection. In keeping with this, MG1 infection of memory CD4+ T cells from HIV-1 infected individuals on HAART also resulted in a significant decrease in inducible HIV-1 gag RNA expression.
By targeting an intracellular pathway that is impaired in latently HIV-infected cells, the findings presented in this dissertation highlight a novel, proof-of-concept approach to eliminate the latent HIV-1 reservoir. Given that VSV 51 and MG1 are currently being studied in cancer clinical trials, there is significant potential to translate this work to in vivo studies.
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Aboagye-Sarfo, Patrick. "Time series analysis of HIV incidence cases in Ghana : trends, predictions and impact of interventions". Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2009. https://ro.ecu.edu.au/theses/1889.
Testo completoAbstract (sommario):
The HIV/AIDS epidemic is one of the world’s leading causes of death, particularly in sub-Saharan African nations like Ghana, and threatens socio-economic development in many developing countries. In this thesis Ghanaian HIV data, comprising monthly number of serologically confirmed reported new HIV cases since 1996, was subdivided into northern and southern sectors based on the geographical location of the ten administrative regions. Potential bias in the collection is considered given the strategic location of the two specialist teaching hospital, one in each sector, which receive referrals from the regions.
Time series modelling was applied to the monthly number of new HIV cases in each sector. Moving average of time series analysis of equal weight was applied to determine the trend for cases of incidence of HIV infection in the northern and southern sectors while Box-Jenkins modelling identification and Holt’s (double) exponential smoothing modelling methods were employed to predict of new incidence of HIV cases for both sectors in respect to sex and age groups. The effectiveness of three existing major interventions was examined using intervention modelling whereas cointegration modelling was used to determine the long-run impact of condom utilisation on the incidence cases of HIV infection. The trend analysis and predictions for the next three years reveal a slow increase in the number of new incidence of HIV cases. Although, various interventions have influenced the number of cases of HIV infection, the magnitude of impact fluctuated and declined with time. The analysis of the long-run impact of condom utilisation, on the reduction of new HIV incidence cases, indicates that new cases of infection will actually increase monthly by factor of 0.4 -0.6 for every 1000 condoms issued. These perplexing results may be because issuing of condoms does not ensure usage.
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Suwisith, Nongluck. "The lived experiences of people living with HIV infection". Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 1996. https://ro.ecu.edu.au/theses/937.
Testo completoAbstract (sommario):
This phenomenological study was undertaken to describe the meaning of living with HIV infection. Descriptive phenomenology was utilised to investigate the lived experiences of persons who had human immunodeficiency virus infection (HIV/ AIDS), describe common elements, themes or patterns of lived experiences of persons with HIV / AIDS, and analyse the meaning of lived experiences of persons with HIV/ AIDS. Twelve Australians, experiencing HIV infection and participating in the community support groups in Perth, volunteered as participants. Two participated in the pilot study. The other ten participants were interviewed individually for the main study. Intensive open-end questions pertaining to the experiences of living with HIV infection were asked during interviews which were audiotaped, transcribed verbatim, and analysed using Colaizzi's (1978) method of analysis. Significant statements were gathered and clustered into themes. Validity and reliability was confirmed during data analysis. The phenomenon of living with HIV infection emerged as experiences of social discrimination, emotional disturbances, changes, losses, suicide attempts, and dealing with the difficulties. The experiences of living with HIV were influenced by chronic illness, terminal illness, and social stigmatisation towards people with HIV. Roy's (1984) Adaptation Model was utilised as a second level for analysis. The Model was able to be applied to explain the experiences of living with IDV to a certain degree. Human responses to a variety of situations showed similar patterns in people living with HIV infection.
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Khati, Makobetsa. "Macrophage-HIV interactions : aptamers against the gp120 surface envelope glycoprotein of the macrophage tropic strains of HIV-1". Thesis, University of Oxford, 2002. http://ora.ox.ac.uk/objects/uuid:a32becf2-bf5d-4428-b598-e8057d977fbd.
Testo completoAbstract (sommario):
HIV-1 has evolved a number of strategies in response to current anti-retroviral drugs and the selection pressure of humoral and cellular immunity. In particular, R5 viral strains that are essential for AIDS pathogenesis are very resistant to neutralization by antibodies. Therefore, the aim of this thesis was to develop synthetic nucleic acid ligands, aptamers, against gp120 of an R5 strain of HIV-1, with a view of using aptamers as novel neutralization molecules and analytical tools to study HIV-1 entry into target cells. The central hypothesis of this thesis was that aptamers by virtue of their small size and slow dissociation rates, compared to antibodies, would easily access and bind occluded gp120 neutralization sites. Using the SELEX protocol and SPR technology, I isolated 2'-Fluoro-pyrimidine-RNA aptamers against HIV-lBa-L monomeric gp120. Most of these aptamers not only bound gp120 with high affinities but also neutralized R5 primary isolates in human PBMC by 1,000 to 100,000-fold, truly unprecedented when compared with natural ligands such as antibodies. Some aptamers, like B4, defined a conserved site of gp120 that could not mutate to escape neutralization following stringent selection, in vitro, for breakthrough virus. This was consistent with subsequent findings that B4 aptatope (binding site) overlaps a poorly immunogenic but highly conserved CD4-induced epitope as determined by competition with 17b and 48d mAbs that map to this neutralization epitope on the gp120. This study was thus the first of its kind to describe neutralization of HIV-1 primary isolates by a ligand against the CD4-induced epitope. Most intriguing, although B4 potently neutralized HIV-1Ba-L infection in PBMC, which is a mixed T cell and macrophage population, it modestly neutralized infection of the same virus in a purified culture of macrophages. These findings are intriguing in that they suggest that aptamers could be used to dissect unique sites on the virus that interact with target cell surface in ways that have not been revealed heretofore, and would help understand better HIV-1 entry pathways, especially in macrophages. Thus neutralizing aptamers such as these could be exploited to provide leads in developing alternative anti-HIV-1 drugs and a deeper understanding of the molecular interactions between the virus and its host cell.
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Prinsloo, Gerhard. "Isolation of an anti-HIV compound from Elaeodendron croceum (Thunb.) DC". Pretoria : [s.n.], 2006. http://upetd.up.ac.za/thesis/available/etd-06082007-164348.
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