Дисертації з теми "Human Immunodeficient Virus"
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1
Wilson, Colleen. "Nurses with human immunodeficiency virus or acquired immunodeficiency syndrome." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=23974.
Повний текст джерелаАнотація:
This thesis will explore the various legal, administrative and ethical issues arising out of the situation in which nurse is HIV-positive or has AIDS. In contrast to the situation of patients suffering from AIDS or HIV, there has been little in the literature, whether legal or medical, on nurses who are infected. The rights and duties of these nurses, testing of nurses for the presence of HIV infection or AIDS and the issue of discrimination are among the matters discussed with reference to relevant legislation and ethical principles.
2
Brettle, Raymond Patrick. "Human immunodeficiency virus : the Edinburgh epidemic." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/20883.
Повний текст джерелаАнотація:
For a variety of socio-economic reasons an epidemic of injection drug use (IDU) involving heroin occurred during the early 1980's in Edinburgh: one third were female, most were young, unemployed and living on large council estates. At the peak of this IDU epidemic, HIV arrived and rapidly spread through this community. By July 1989 over 1000 individuals or 0.1% of the population of Lothian (750,000) had been recognised to have been infected with HIV, the majority via IDU. This is of the same order as the worst affected region in England (North West Thames). The majority of these individuals however live in the City of Edinburgh with a population of only around 300,000 (1981 census). Consequently a realistic prevalence for this population is actually 0.3% or 3 times the worst affected English region. Thus this new area of medicine has considerable relevance for future medicine in Edinburgh and Scotland. The thesis describes the disease, the epidemiology of Injection Drug Use and IDU related HIV and the early epidemic in Edinburgh. It also describes the clinical services that were developed at the City Hospital in Edinburgh and the problems that this new service encountered. The provision of health care for this difficult patient population facilitated a variety of research projects. The thesis describes some of the results of these projects particularly those concerned with natural history, clinical presentation and use of antiretroviral therapy in IDU related HIV. Lastly the factors found to affect the transmission of HIV to the heterosexual partners of the patients are presented together with their relevance for other populations.
3
Walker, S. M. "Transactivation of human immunodeficiency virus by human cytomegalovirus." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387104.
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4
Cochrane, Alexandra. "Human immunodeficiency virus infection of CD8 lymphocytes." Thesis, University of Edinburgh, 2006. http://hdl.handle.net/1842/24468.
Повний текст джерелаАнотація:
To confirm that CD8 lymphocytes are infected with HIV in vivo, and to investigate the mechanism of infection, HIV long terminal repeat (LTR) DNA was quantified in CD8 lymphocyte subsets of known purity, isolated from the blood of 20 subjects with HIV infection. HIV LTR was demonstrated in CD8 lymphocytes of 18/20 subjects, and in the subjects with chronic infection the frequency of infection increased with disease progression. HIV infection of CD8brightCD4dim lymphocytes was significantly more frequent (median 1197 HIV LTR copies / million cells) than that of CD8+CD4- lymphocytes (undetectable in 7/9 subjects, p<0.01) suggesting infection on activation rather than during intrathymic development. The level of infection in the CD8brightCD4dim lymphocytes approached that in CD4 lymphocytes from the same subjects (median 3660 HIV LTR copies / million cells) and therefore could not be explained by CD4 lymphocyte contamination. Given the high level of infection of CD8brightCD4dim lymphocytes their prevalence and phenotype was assessed in 8 healthy and 16 HIV infected subjects. The proportion of CD8 lymphocytes with a CD8brightCD4dim phenotype ranged from 0.3 to 3.4% with no significant difference between HIV infected and healthy subjects. The majority displayed a CD45RA-ve CD27+ve (memory) phenotype, but in contrast to the populations generated in vitro, the circulating population was not uniformly activated but rather comprised both activated and quiescent cells. Thus HIV infected CD8 lymphocytes commonly circulate in HIV infected subjects, and are likely to be infected on activation rather than during intrathymic development. Given that a proportion of the circulating CD8brightCD4dim lymphocytes have a quiescent phenotype, they may act as a long lived reservoir with implications for viral eradication.
5
Langeni, Delile Gertrude. "Self-Disclosure of Human Immunodeficiency Virus Status in Personal Relationships: Perceptions of South Africans Living with Human Immunodeficiency Virus." ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/4798.
Повний текст джерелаАнотація:
Despite enormous research on the experience of living with HIV, many questions remain regarding self-disclosure of HIV status to sexual partners by people living with HIV (PLWHIV), which is essential to reducing further infection. In this study, a phenomenological approach captured the experience of self-disclosure among South Africans living with HIV in Louwsburg, South Africa. The health belief model served as a theoretical framework, and in-depth interviews were conducted with 12 PLWHIV (8 women, 4 men) who self-disclosed their HIV status to their sexual partners. Their experiences were explored, discovering their illness, motives for self-disclosure, feelings regarding disclosing, responses of their sexual partners, their emotional reaction, and about their medical care. The themes rose from interviews showed that (a) many PLWHIV are reluctant to self-disclose until they actively experienced health issues; (b) motives for disclosure include the wish to ensure fairness; support and to empower other PLWHIV to prevent further infection; (c) feelings of disclosure are primarily relief and liberation, even though risks remain, especially for families separated by labor migration laws; (d) the response of sexual partners to disclosure varies widely; some are motivated to get tested and use condoms, decline and respond only with anger, blame, even abandonment; and (e) after accessing medical care, most PLWHIV reported support and appearing less sick, which reduces social stigma. The women were more open, forthcoming, and transparent about disclosing than men participants. Findings will assist with the creation of future health education programs aimed at creating safe environments to disclose HIV status, which may reduce community risk of contracting the virus.
6
Pise-Masison, Cynthia Ann. "Human Immunodeficiency Virus Type-1 Infection of Human Myeloid Cells." eScholarship@UMMS, 1994. https://escholarship.umassmed.edu/gsbs_diss/87.
Повний текст джерелаАнотація:
Infection with human immunodeficiency virus type 1 (HIV-1) results in a wide range of immunologic and hematopoietic abnormalities. The overall goal of this dissertation was directed toward obtaining a better understanding of the interactions of HIV-1 and myeloid cells in relation to the pathogenesis of AIDS. The human myelomonocytic cell line, HL-60, was used as a model system to determine if HIV-1 infects myeloid progenitor cells and subsequently, if infection affects their differentiation. HL-60 cells and the human prototypic T cell line, H9 were infected with three different HIV-l isolates (IIIB, PM213, and NL4-3) which are known to infect T cells. All three isolates productively infected both H9 and HL-60 cells; however, HIV-1 antigen expression and cytopathicity was delayed by approximately 15 days in infected HL-60 cells compared H9 cells. To examine the effect of HIV-l infection on myeloid differentiation, chronically infected HL-60 cells and clonal lines derived from them were induced to differentiate into either granulocytes by treatment with dimethyl formamide (DMF) or into monocytes by treatment with phorbol l2-myristate 13 acetate (PMA). By both cellular morphology and function, approximately the same percentage of treated, HIV-infected HL-60 cells differentiated into either granulocytes or monocytes as treated, control HL-60 cells. Taken together, these results indicate that HIV-1 infection does not affect the morphological or functional differentiation of HL-60 cells.
In an effort to understand the differences in the regulation of HIV-l infection in myeloid versus T cells, the life cycle of NL4-3 was examined in HL-60 cells and H9 cells. Initially, NL4-3 replication was restricted in HL-60 cells compared to H9 cells. This restriction was overcome 15 days after infection by the generation of a viral isolate, NL4-3(M). NL4-3(M), harvested during the lytic phase of NL4-3 infection of HL-60 cells, caused cell death approximately 8 days after infection in both H9 and HL-60 cells. Although measurements of viral entry kinetics demonstrated that the timing of entry of NL4-3 and NL4-3(M) in HL-60 cells and NL4-3 in H9 cells was similar, a quantitative polymerase chain reaction (PCR) analysis of newly reverse transcribed NL4-3 DNA in H9 and HL-60 cells revealed that NL4-3 infected H9 cells and NL4-3(M) infected HL-60 cells contain consistently higher amounts of newly reverse transcribed DNA than NL4-3 infected HL-60 cells. The delay in NL4-3 replication in HL-60 cells was further amplified by inefficient spread of the virus throughout the HL-60 culture as measured by RNA production and DNA integration suggesting that another step in the viral life cycle after reverse transcription was also restricted. These results suggest that the efficiency of NL43 replication in HL-60 cells is restricted at several steps in the viral life cycle. Further, these restrictions are overcome by the generation of a viral variant, NL4-3(M), which efficiently replicates in myeloid cells.
The tropism of NL4-3(M) was further characterized by testing its growth in monocyte-derived macrophages (MDM). Unlike NL4-3, NL4-3(M) productively infected MDM cultures. The ability of NL4-3(M) to infect macrophages was conferred by the envelope gene. This was demonstrated by the ability of the recombinant virus, NL4-3envA, which contains the envelope of NL4-3(M) in the context of the NL4-3 genome, to infect and replicate in MDM cultures. The envelope gene of NL4-3(M), however, did not confer ability to rapidly kill HL-60 cells. Together, these findings demonstrate that viral determinants controlling entry into MDM are different trom the determinants controlling the cytopathic phenotype in HL-60 cells.
7
Loo, Ryan K. "Sampling Considerations in Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome Needs Assessments." DigitalCommons@USU, 2003. https://digitalcommons.usu.edu/etd/6179.
Повний текст джерелаАнотація:
The human immunodeficiency virus (HIV) reduces the number of healthy immune cells in the human body. When the immune cells drop below a certain level, the person is diagnosed as having acquired immunodeficiency syndrome (AIDS), which increases the likelihood of opportunistic infections. As a result, people living with HIV I AIDS (PL WH/ A) have an elevated need for medical and support services. HIV I AIDS needs assessments identify unmet needs, and the results are used in the allocation of resources. Failure to accurately identify needs due to nonrepresentative samples may result in PL WH/ A failing to receive needed services. Random sampling is rarely used, but convenience sampling may provide representative samples if the principles of generalization are followed. The purpose of this study was to assess the degree to which lack of representation is occurring, to assess the impact of lack of representation, and to explore ways to improve the representative qualities of a sample.
8
Shi, Ruili. "Biological studies on inhibitors of human immunodeficiency virus." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0024/NQ37913.pdf.
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9
McKiel, Vanessa. "Cytokine-induced alterations in human immunodeficiency virus multiplication." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=55512.
Повний текст джерелаАнотація:
The ability of the human immunodeficiency virus (HIV) to replicate in T-cells and macrophages has been shown to be influenced by immunomodulatory cytokines; furthermore, HIV infection of these cells can alter the kinetics of cytokine transcription. We found that chronic HIV IIIB infection of myelomonoblastic PLB 985 cells resulted in an altered pattern of type 1 interferon (IFN) transcription. Paradoxically, despite the antiviral effects of IFN, HIV-induced dysregulation of IFN transcription may actually lead to the establishment of a cellular environment that supports a chronic infection.Since HIV replication is dependent on cellular activation, immunosuppressive cytokines which deactivate T-cells and macrophages may be important modulators of an antiviral effect. We previously demonstrated the anti-HIV effects of IFN$ alpha$2, alone and in a cooperative combination with 3$ sp prime$-azido-2$ sp prime$3$ sp prime$-dideoxythymidine (AZT), in limiting the expression of HIV IIIB in promonocytic U937 cells. We further tested the anti-HIV potential of the immunosuppressive cytokines transforming growth factor beta (TGF-$ beta$1) and interleukin-10 (IL-10), alone and in combination with AZT. TGF-$ beta$1 as a single agent had no effect on the multiplication of HIV IIIB in de novo infected PLB 985 cells; however, co-treatment with TGF-$ beta$1 and AZT synergistically slowed virus multiplication within the first week following infection. The synergistic actions of TGF-$ beta$1 and AZT were also observed in PLB 985 cells infected with an AZT-resistant strain of HIV-1. In contrast, IL-10 seemed to enhance HIV IIIB multiplication in PLB 985 cells. These antiviral treatments had no inhibitory effect on HIV IIIB multiplication in the T-cell line Jurkat. Elucidation of the role of cytokines in controlling the degree of HIV multiplication may have an impact on both clinical treatments and understanding the progression to AIDS.
10
Harrison, Thomas Stephen. "Interactions between Human Immunodeficiency Virus and Cryptococcus neoformans." Thesis, St George's, University of London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299059.
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11
Chua, Ser Ling. "Papular pruritic eruption of human immunodeficiency virus infection." Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/30750/.
Повний текст джерелаАнотація:
Background Papular pruritic eruption (PPE) of human immunodeficiency virus (HIV) infection is common HIV-infected populations who live in tropical and subtropical regions. It is characterized by chronic and intensely itchy papules that are usually more highly concentrated on the extremities, adversely impacting on quality of life. Its aetiology has been postulated to be an altered and exaggerated immunological response to insect bites or stings. It has been reported to diminish in severity or resolve with antiretroviral therapy (ART). Its presence after at least six months of ART has been proposed as one of several clinical markers of failure of antiretroviral treatment. Objectives 1. To systematically summarise the evidence of interventions for PPE 2. To translate, culturally adapt, and test oral administration of a Runyankore-version of Skindex-16 for use in dermatology research in Mbarara, Uganda 3. To determine factors associated with PPE in HIV-infected Ugandan adults receiving ART for at least 15 months 4. To describe the natural history of PPE in HIV-infected Ugandan adults over two years from the time of ART initiation and explore the association between recurrent or persistent PPE and antiretroviral treatment failure Methods Systematic review of interventions for PPE Electronic searches of Medical Literature Analysis And Retrieval System Online (Medline), Excerpta Medica Database (Embase), Cumulative Index To Nursing And Allied Health Literature (CINAHL), Global Health Library, Cochrane Library, World Health Organization (WHO) International Clinical trials registry and National Library Of Medicine (NLM) gateway were carried out from January 1980 to July 2014. Studies of any design were included. The primary outcome measure for this review was resolution of skin disease. The quality of evidence was assessed using the Newcastle-Ottawa quality assessment scale and Grading Of Recommendation, Assessment, Development And Evaluation (GRADE) approach, where appropriate. Two authors carried out data extraction and quality assessment of studies independently. Runyankore-version of Skindex-16 for oral administration in Mbarara, Uganda Skindex-16 in English was translated to Runyankore, and then back-translated to English. The original and back-translated versions of Skindex-16 were compared for fidelity of translation. The Runyankore-version was administered orally to 47 dermatology patients and 47 random hospital visitors. Study participants were also asked about the characteristics of their skin condition including its duration, presence of skin colour change and ease or difficulty of concealment as well as an open question on how their skin condition has affected them. Case control study examining factors associated with PPE in the ART era This is a case–control study nested within a 515-person cohort receiving care at the HIV clinic of a teaching hospital in Mbarara, Uganda. Forty-five cases and 90 controls were enrolled. Cases had received ART for ≥15 months, fulfilled the clinical case definition of PPE and had skin biopsy findings consistent with PPE. Each case was individually matched with two controls for age, sex and ART duration. Cohort study describing the natural history of PPE over two years from ART initiation This is a cohort study of HIV-infected Uganda adults initiating ART and receiving care at the HIV clinic of a teaching hospital in Mbarara, Uganda who fulfilled the clinical case definition of PPE and had skin biopsy findings consistent with PPE. Standardised interviews, clinical photography, HIV viral load, CD4 counts and CD8+ T-cell activation markers were measured at three-month intervals for two years. Results Systematic review of interventions for PPE No randomised controlled trials were identified. Thirteen studies with a total 188 participants were included. ART was associated with resolution of PPE in a prospective observational study that had high loss to follow-up rates. Two observational studies reported positive responses of PPE to oral antihistamines (promethazine and cetirizine). Pentoxifylline was associated with diminished signs and symptoms of PPE in an uncontrolled open trial and superior to dapsone and a combination of antihistamine and topical corticosteroids in a parallel group non-randomised trial. Resolution of PPE was reported with a combination of topical corticosteroids and oral antihistamines in a case report. The efficacy of ultraviolet B (UVB) phototherapy was reported in an observational study with eight participants and three case studies with a total of five participants. Runyankore-version of Skindex-16 for oral administration in Mbarara, Uganda Oral delivery was feasible, taking ≤10 minutes per subject. High Cronbach α values (0.86, 0.88 and 0.85 for Symptoms, Emotions and Functioning subscales, respectively) demonstrated internal consistency reliability. As hypothesised, subjects with reported skin problems, dyspigmentation and difficulty in concealment had higher mean Skindex-16 scores, indicating construct validity. A large proportion (72.4%) of responses to the open-ended question were addressed in Skindex-16, indicating content validity. Case control study examining factors associated with PPE in the ART era Twenty-five of 45 cases (56%) had histological findings consistent with PPE (known as PPE cases). At skin examination and biopsy (study enrolment), a similar proportion of PPE cases and their matched controls had plasma HIV RNA <400 copies/ml (96% vs. 85%, p=0·31). The odds of having PPE increased four-fold with every log increase in viral load at ART initiation (p=0.02) but not at study enrolment. CD4 counts at ART initiation and study enrolment, and CD4 gains and CD8 T-cell activation measured 6 and 12 months after ART commencement were not associated with the presence of PPE. Study participants who reported daily insect bites had greater odds of being cases [odds ratio (OR) 8.3, p<0.001] or PPE cases (OR 8.6, p=0.01). Cohort study of natural history of PPE over 2 years from ART initiation Seventeen (15 female and 2 male) participants with a median age of 29.8 years were enrolled. Median CD4 count and HIV viral load at ART commencement was 108 cells/mm3 and 114,442 copies/ml, respectively. Resolution of PPE occurred in 13 of 17 (76%) study participants at a median time of 8.5 months after ART initiation, although PPE recurrence was observed at seven participants during the study period. Two participants had persistent PPE. Virological failure was not detected in any study participant. HIV RNA was less than 400 copies/ml at a median time of three months from ART initiation in all study participants. Conclusions 1. The evidence base of interventions for PPE is of low quality. There is some evidence of the efficacy of ART in the management of PPE. Pentoxifylline and phototherapy may have a role in its management but are unlikely to be available in resource-limited settings. Oral antihistamines and topical corticosteroids may be helpful in some individuals affected by PPE. 2. The orally administered Runyankore-version of Skindex-16 is reliable, with construct and content validity, and feasible for use in dermatology research in Mbarara, Uganda. 3. PPE in HIV-infected Ugandan adults receiving ART for at least 15 months was associated with reported daily insect bites and greater HIV viraemia at ART commencement, independent of CD4 count. 4. Recurrent or persistent PPE in HIV-infected Ugandan adults observed over two years from initiation of ART was not associated with virological failure in participants of this study.
12
Gao, Zhanhai School of Mathematics UNSW. "Modelling Human Immunodeficiency Virus and Hepatitis C Virus Epidemics in Australia." Awarded by:University of New South Wales. School of Mathematics, 2001. http://handle.unsw.edu.au/1959.4/18187.
Повний текст джерелаАнотація:
This thesis is concerned with the mathematical modelling for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) epidemics in Australia. There are two parts to this thesis. Part I is aimed at modelling the transmission of HIV and HCV via needle sharing among injecting drug users (IDUs). The dynamical model of an epidemic through needle sharing among IDUs is derived. This model reveals the correlation between needle sharing and the epidemic prevalence among IDUs. The simulations of HIV and HCV prevalence and incidence among IDUs in Australia are made with this model. The comparison of simulated results with literature estimates shows that the modelled results are consistent with the literature estimates. The effects of needle sharing and cleaning on HIV and HCV prevalence and incidence among IDUs in Australia are evaluated. Part II is devoted to modelling the spread of HIV in the general community in Australia. A mathematical model is formulated to assess the epidemiological consequences of injecting drug use and sexual transmission in Australia. The effects of highly active antiretroviral therapies (HAART) on the HIV epidemic are included. The modelled results are in broad agreement with the literature estimates and observed data. The long-term effects of HAART are also discussed.
13
Heusinger, Elena [Verfasser]. "Preadaptation of Simian Immunodeficiency Virus SIVsmm Facilitated Env-Mediated Counteraction of Human Tetherin by Human Immunodeficiency Virus Type 2 / Elena Heusinger." Ulm : Universität Ulm, 2019. http://d-nb.info/1177882604/34.
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14
Ollerton, Matthew T. "Capacity of Human Immunodeficiency Virus Targeting Chimeric Antigen Receptor T Cells to Eliminate Follicular Dendritic Cells Bearing Human Immunodeficiency Virus Immune Complexes." BYU ScholarsArchive, 2017. https://scholarsarchive.byu.edu/etd/7240.
Повний текст джерелаАнотація:
An important obstacle to a functional cure for HIV/AIDS is the persistence of viral reservoirs found throughout the body in various cells and tissues. Reservoirs can be latently infected cells, or in the case of follicular dendritic cells (FDC), non-infected cells that trap infectious virus on their surface through immune complexes (HIV-IC). Although several strategies have been employed to target and eliminate viral reservoirs, they are short-lived and ineffective. In an attempt to provide a long-term approach, chimeric antigen receptor T (CAR-T) cells were designed to eliminate native HIV on FDCs. Although effective at eliminating HIV-infected cells, and halting spreading infection, their ability to eliminate the viral reservoir found on (FDCs) remains unclear. We used a novel second-generation CAR-T cell expressing domains 1 and 2 of CD4 followed by the mannose binding lectin (MBL) to allow recognition of native HIV envelope (Env) to determine the capacity to respond to the viral reservoir found on FDCs. We employed a novel fluorescent lysis assay, the Carboxyfluorescein succinimidyl ester (CFSE) release assay, as well as flow cytometric based assays to detect functional CAR-T activation through IFN-γ production and CD107a (i.e., LAMP1) membrane accumulation to test cytolytic capacity and functional activation of CD4-MBL CAR-T cells, respectively. We demonstrated their efficacy at eliminating HIV-infected cells or cells expressing gp160. However, these CAR-T cells were unable to lyse cells bearing surface bound HIV-IC. We found that failed lysis was not a unique feature of a resistant target, but a limitation in the CAR-T recognition elements. CAR-T cells were inactive in the presence of free HIV or in the presence of concentrated, immobilized virus. Further experiments determined that in addition to gp120 recognition by the CAR-T, the adhesion molecule ICAM-1 was necessary for efficient CAR-T cell killing of HIV-infected cells. CAR-T cell activity and killing were inhibited in the presence of ICAM-1 blocking antibody. These results suggest that other factors, such as adhesion molecules, play a vital role in CAR-T responses to HIV-infected cells. In addition, our findings highlighted the necessity to consider all models of HIV reservoirs, including FDCs, when evaluating therapeutic efficacy.
15
Li, Yan. "Processing and secretion of human immunodeficiency virus glycoprotein,gp120." Thesis, University of Ottawa (Canada), 1992. http://hdl.handle.net/10393/10962.
Повний текст джерелаАнотація:
The natural signal sequence of HIV-1 gp120 contains an unusually long hydrophobic domain and five positively charged amino acids. When the gp120 gene was cloned into a baculovirus expression vector under the control of the baculovirus polyhedrin gene promoter, it exhibited an extremely low level of secretion. However, deletion of the signal sequence resulted in the production of large quantities of a nonglycosylated form of gp120 and fusion of honeybee melittin or murine interleukin 3 signal sequences, which contain only one or no positively charged residues, respectively, resulted in a high level of expression as well as glycosylation and secretion. Four charge-altered signal mutants were generated by oligonucleotide-directed mutagenesis. Positively charged amino acids in the natural signal sequence were substituted with neutral amino acids. The results of these experiments showed that the expression and secretion of gp120 was progressively increased by decreasing the positive charge in a stepwise fashion from + 5 to + 3, + 2, and + 1. However, elimination of all five positive charges (leaving a net negative charge of -1 at the NH 2 terminus) caused accumulation of large amounts of a nonglycosylated form of gp120 but decreased the amounts of glycosylated forms of gp120. These signal peptide mutants clearly demonstrate that the positively charged amino acids in the natural signal sequence of HIV-1 gp120 are key factors determining its poor expression and secretion in insect cells. Analysis of intracellular transport and folding of gp120 further indicates that the highly charged uncleaved signal peptide rather than disulfide bond formation is an important factor limiting transport of gp120 from the rough endoplasmic reticulum (RER) to the Golgi apparatus; its presence affects gp120 folding and slows its rate of transport to the cell surface. The requirement for carbohydrate on HIV gp120 in CD4 binding has been the subject of much debate. There have been conflicting reports regarding the role of gp120 glycans in binding to CD4. An important question is whether the carbohydrate itself plays an important role in this interaction. Nonglycosylated and glycosylated forms of gp120 from HIV-1 and HIV-2 were produced using the baculovirus expression system and their CD4 binding properties were determined. The nonglycosylated forms of gp120 generated by either deletion of the signal sequence or synthesized in the presence of tunicamycin failed to bind to CD4. In contrast, highly mannosylated recombinant gp120 bound well to soluble CD4. Enzymatic removal of carbohydrate chains from glycosylated gp120 by endoglycosidase H (endo H) or by a mixture of endoglycosidase F and N-glycanase (endo FNG) in the presence or absence of SDS had little or no effect on the ability of gp120 to bind CD4. The data indicate that carbohydrate chains per se do not play a significant role in interaction between gp120 and CD4 molecules but that N-linked glycosylation is required for correct protein folding that provides the proper conformation for CD4 binding. Analysis of intracellular folding of gp120, using its ability to bind CD4 as a functional assay for overall conformation, further supports the hypothesis that N-linked glycosylation of HIV gp120 plays an essential role in promoting either the correct folding of the protein or in its stabilization.
16
Zeibdawi, Abdul-Rahman. "Recombinant human immunodeficiency virus reverse transcriptases, activity and fidelity." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq20986.pdf.
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17
Yim, Chi-ho Howard. "Cytokine dysregulation by human immunodeficiency virus-1 transactivating protein." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36987700.
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18
Brasey, Ann. "Translation regulation of the Human Immunodeficiency Virus type 1." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85890.
Повний текст джерелаАнотація:
Viruses are among the ultimate conquerors. Even the exploits of Genghis Khan and Alexander the Great seem pale when compared to viral feats. To give but one example, over the last 50 years, the human immunodeficiency virus (HIV) has swept across six continents, now claiming several million lives yearly. Despite sustained intense research efforts, there is still no treatment to eradicate HIV infection.For billions of years, viruses evolved strategies to enter and take control of organisms to generate progeny viruses. Eukaryotic cell viruses developed various means of hijacking the cellular protein synthesis machinery. Understanding these mechanisms opens a unique window of opportunity: that of eventually being able to specifically inhibit virus protein production. In this context, we investigated how HIV-1 translation is regulated. This work initially characterizes an RNA structural element in the HIV-1 leader able to directly recruit the protein synthesis machinery, i.e. an internal ribosome entry site (IRES). This element is capable of driving protein synthesis during the G2/M cell-cycle phase when cap-dependent translation is inhibited.
Several virus families use IRESs. IRES-dependent translation usually involves a subset of the factors implicated in cellular protein synthesis. However, toeprinting studies suggest that HIV-1 requires factors different from the canonical translation initiation factors to initiate protein synthesis. HeLa cell protein fractionation studies identified p97, an eIF4G homolog, its apoptotic cleavage product, p86, and a novel protein, ropp120, as putative HIV-1 transactivators. Further testing revealed that these proteins do not directly stimulate HIV-1 leader dependent translation. Experiments also showed that La autoantigen, another likely HIV-1 IRES transactivator candidate, does not directly stimulate HIV-1 dependent translation.
The last portion of this work investigates the interplay of the HIV-1 IRES with cap structures, polyA tails and the HIV-1 3'UTR region since these elements are present on the viral genomic RNA. We found that the HIV-1 leader does not synergize nor does it interfere with the translation stimulation mediated by the cap, the polyA and the HIV-1 3'UTR. Data presented herein suggest that the HIV-1 leader is an IRES able to shunt initiation complexes from the cap structure to drive protein synthesis.
19
Zemmel, Rodney W. "Rev-RRE interactions in human immunodeficiency virus gene expression." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390234.
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20
Yim, Chi-ho Howard, and 嚴志濠. "Cytokine dysregulation by human immunodeficiency virus-1 transactivating protein." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B36987700.
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Reeves, Jacqueline Denise. "CD4-independent infection by human immunodeficiency virus type 2." Thesis, Institute of Cancer Research (University Of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368031.
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Khiytani, Dheeraj K. "Pre-integration complexes of human immunodeficiency virus type 1." Thesis, University of Warwick, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247285.
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Willey, Samantha. "Cellular tropism of human immunodeficiency virus : receptors and inhibitors." Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404902.
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Boffito, Marta. "Clinical pharmacology of human immunodeficiency virus-1 protease inhibitors." Thesis, University of Liverpool, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.403237.
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Jones, Christopher P. "Primer tRNA annealing by human immunodeficiency virus type 1." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1337962197.
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Burnett, Mary Susan. "Development of a live vaccine for human immunodeficiency virus /." Digital version accessible at:, 1997. http://wwwlib.umi.com/cr/utexas/main.
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Cook, Scott C. "Human immunodeficiency virus : determining predictors of unsafe sexual behavior /." free to MU campus, to others for purchase, 1999. http://wwwlib.umi.com/cr/mo/fullcit?p9962514.
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Jordán, de Paiz Ana. "Synonymous changes in the human immunodeficiency virus genome as a strategy to study virus biology." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/669843.
Повний текст джерелаАнотація:
La recodificación sinónima de los genomas se ha usado ampliamente para estudiar diferentes aspectos de la biología de los virus. Esta herramienta se basa en modificar la secuencia de nucleótidos de un gen sin cambiar la secuencia de aminoácidos, es decir, la secuencia de la proteína no se ve afectada. Estudios previos han demostrado atenuación viral debida a una reducción en la expresión proteica después de llevar a cabo la recodificación sinónima. De la misma manera, esta herramienta ha permitido la identificación de estructuras secundarias del ARN, la descripción de factores virales o interacciones con el sistema inmune innato, así como desentrañar la regulación temporal de los genes virales. En este trabajo hemos recodificado sinónimamente los genes de la proteasa y de la envuelta (Env) del Virus de Inmunodeficiencia Humana 1 (HIV-1). Comparamos el desarrollo de resistencias del HIV-1 a inhibidores de la proteasa (IPs) entre el virus salvaje (WT) y un virus sintético (MAX) que lleva una secuencia de la proteasa recodificada en el uso de pares de codones incluyendo 38 mutaciones sinónimas (13%). Los virus WT y MAX no muestran diferencias replicativas. Ambos virus fueron propagados en células MT-4 con la presión selectiva a dos IPs atazanavir (ATV) y darunavir (DRV). Tanto el virus WT como el MAX desarrollaron resistencias fenotípicas a IPs. Análisis clonales de secuenciación masiva revelaron que ambos virus desarrollaron mutaciones de resistencia a ATV y DRV previamente descritas. Sin embargo, las resistencias que desarrollaron las proteasas WT y MAX eran diferentes entre ambas variantes. Nuestros resultados indican que la proteasa recodificada del HIV-1 mostró una robustez y evolvabilidad similar al WT, pero la posición en el espacio de secuencias delinea la evolución de cada espectro mutante. Para estudiar cómo las mutaciones sinónimas afectan a la replicación viral, se diseñaron mutantes de Env que cambiaban el uso de codones y el uso de pares de codones; el número de dinucleótidos CpG también se alteró. La variante sintética del virus Recoded-env resultó letal para la viabilidad del VIH-1 después de cambiar su uso de codones mediante la modificación de 39 nucleótidos (1,5%). Análisis de expresión proteica revelaron que la traducción se había modificado en Recoded-env. Varios mutantes se diseñaron basados en Recoded-env para investigar la letalidad de este mutante. Uno de ellos, Recoded_env_3’Bwt, sólo revirtió a WT dos mutaciones de un mismo codón, el codón 34, localizado en la región codificante gp41. Es de resaltar que esta variante del virus no mostró diferencias en replicación en células MT-4 o PBMCs ni una reducción dramática en expresión proteica en comparación con el WT. El análisis de secuencias de gp41, donde se encuentra localizado el codón 34, demostró que la estructura secundaria del ARN estaba severamente interrumpida en Recoded-env. De la misma forma, después de cambiar el uso de pares de codones de env, se generaron
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diferentes variantes que optimizaban, deoptimizaban o mantenían neutro el sesgo de pares de codones (CPB). Estas variantes confirmaron la importancia de las sustituciones sinónimas en la región codificante de gp41. Solo una de estas variantes, MinCpG.2, era viable con la región gp41 mutada. Se encontraron diferencias en esta región entre MinCpG.2 y el resto de variantes CPB que explicaban la letalidad. También observamos que dos variantes virales que tenían un CPB optimizado, Max-3’wt y MaxCpG-3’wt, mostraban una capacidad replicativa significativamente reducida cuando se comparó con el WT. Además, las variantes de CPB con diferentes proporciones de CpGs nos permitieron concluir que, en nuestro modelo, un número elevado de CpGs no atenuaba el virus. Nuestros resultados confirman que la recodificación sinónima de un gen o genoma es una herramienta muy útil para descifrar diferentes aspectos de la biología viral.Synonymous genome recoding has been widely used to study different aspects of viral biology. It is based on modifying the nucleotide sequence of a gene without changing the amino acid sequence, thus the protein sequence is not affected. Previous studies have demonstrated viral attenuation by reduction in protein expression after synonymous recoding. Likewise, this tool has allowed the identification of RNA secondary structures, the description of viral factors or interactions with the innate immune system, as well as unravelling the temporal regulation of viral genes. Here, we synonymously recoded the Human Immunodeficiency Virus 1 (HIV-1) protease and envelope genes. We compared the development of HIV-1 resistance to protease inhibitors (PIs) between wild-type (WT) virus and a synthetic virus (MAX) carrying a codon pair re-engineered protease sequence including 38 (13%) synonymous mutations. WT and MAX viruses showed indistinguishable replication. Both viruses were subjected to serial passages in MT-4 cells with selective pressure from the PIs atazanavir (ATV) and darunavir (DRV) and they both developed phenotypic resistance to PIs. Ultra-deep sequence clonal analysis revealed that both viruses harbored previously described resistance mutations to ATV and DRV. However, the WT and MAX virus proteases showed different resistance variant repertoires. Our results indicate that HIV-1 recoded protease showed similar mutational robustness and evolvability to WT, but the position in sequence space delineates the evolution of each mutant spectra. To study how synonymous mutations affected virus replication, Env mutants were designed by changing its codon usage and codon pair usage. In addition, the number of CpG dinucleotides were also altered. The synthetic Recoded-env virus variant was lethal for HIV-1 after changing its codon usage by synonymously altering 39 nucleotides (1,5%). Protein expression analyses revealed that translation was modified in Recoded-env. Several mutants were designed based on Recoded-env to further investigate the lethality of this mutant. One of them, Recoded_env_3’Bwt, only reverted to WT two mutations of the same codon, named codon 34, located in gp41 coding region. Interestingly, this virus variant did not show significant differences in replication capacity both in MT-4 cells and PBMCs nor a dramatic decrease in protein production, when compared to WT. Analyzing sequences of gp41 in which codon 34 is located, we concluded that the WT RNA secondary structure was severely disrupted in Recoded-env. Similarly, after changing env codon pair usage, different virus variants which optimized, deoptimized or maintained neutral the codon pair bias (CPB) confirmed the relevance of synonymous substitutions in gp41 coding region. Only one of the virus variants, MinCpG.2, was replicative without reverting gp41 to WT. Differences in this region were found between MinCpG.2 and the rest of the designed CPB variants that 16 explained their lethality. We also observed that two virus variants, Max-3’wt and MaxCpG-3’wt, had significantly lower replication capacity when compared to WT although they had an optimized CPB. Moreover, the CPB virus variants with different number of CpGs allowed us to conclude that, in our model, increasing the number of CpGs did not attenuate the virus. Overall, our results confirmed that synonymous recoding a gene or genome is a useful tool to unravel different aspects of the virus biology.
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Scholes, Andrea Gwendoline Mary. "Effect of human immunodeficiency virus infection on oral shedding of human herpesviruses." Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295830.
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Meys, Rhonda. "Aspects of human papillomavirus (HPV) disease in human immunodeficiency virus (HIV) infection." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/10730.
Повний текст джерелаАнотація:
Cutaneous and genital human papillomavirus (HPV) infection in HIV patients, on suppressive anti-retroviral therapy (ART), poses under-investigated clinical challenges. HPV in HIV may represent a form of immune reconstitution associated disease (IRAD). HPV disease and IRADs have been separately correlated with human leucocyte antigen (HLA) genotype. HLA might also influence HPV in HIV. Comprehensive HPV typing of persistent warts obtained from HIV infected and healthy subjects was performed. Cutaneous HPV types were detected using nested PCR/sequencing and newly developed (Luminex based) HSLPCR/ MPG; genital and beta HPV types were identified using a reverse hybridisation line probe assay. Real time PCR was employed to determine HPV DNA viral loads. HLA alleles were defined in HIV infected and healthy patients by Luminex-based molecular typing using DNA derived from blood. The HPV profile of cutaneous and genital HIV warts differs significantly from warts from healthy individuals. In HIV, HPV 7 has been confirmed to be an important HPV type in cutaneous warts (p=0.001). In genital warts in HIV, HPV 11 is the predominant HPV type (p=0.15) and HPV 6 is less common (p=0.002), contrasting with the usual finding that HPV 6 is the principal type in the general population. Cross-over of HPV types between cutaneous and genital sites suggests that HPV tropism is less important than previously thought. An excess of beta HPV types, predominantly as mixed infections, is seen in cutaneous warts in HIV (p<0.0005). The HLA class I allele group HLA-B*44 (as the allele HLA-B*44:02 and the haplotype HLA-B*44, -C*05) has been identified more frequently in HIV than in controls (p=0.004, allele group; p=0.0006, allele; p=0.001, haplotype). The class II allele HLA-DQB1*06 may also be of interest (p=0.03). However, the differences are reduced after correction for multiple testing. Further work is required to ascertain if these HPV types and alleles are of importance.
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Mboto, Clement Ibi. "Studies on Human Immunodeficiency Virus and hepatitus C virus coinfection in the Gambia." Thesis, Kingston University, 2005. http://eprints.kingston.ac.uk/20370/.
Повний текст джерелаАнотація:
Co-infection with Hepatitis C Virus (HCV) is a common occurrence in Human Immunodeficiency Virus (HIV)-positive patients and an increasing cause of morbidity and mortality. Little is known however of the burden or the natural history of these infections or their interactions in most parts of sub-Saharan Africa, where both viruses are endemic. In this study a total of 1500 people aged 11 months to 76 years referred to the serology unit of Royal Victoria Teaching Hospital between the months of July to December 2003 were evaluated for anti-HIV, anti-HCV and CD4+ T-cell count and compared with the subjects' socio-demographic and risk factors. HIV and HIV/ HCV seropositive persons who consented to a follow-up study were age and sex matched with HIV and HCV seronegative control subjects and followed for 18 months with biannual monitoring of trends in CD4 count against a possible HIV or HCV seroconversion of the seronegative control subjects. The overall prevalence of antibodies to HIV and HCV was 6.7% (101/1500) (Cl, 5.6-8.2) and 2.1% (31/1500) (95 % CI, 1.4-2.9) respectively. HIV rates in asymptomatic adults were 3.6 %( 43/1189) (OR: 0.16; Cl: 0.13-0.28) and 1.0 %( 12/1189 (OR: 0.16; Cl: 0.08-0.34) for HCV. HIV/HCV co-infections rate was 0.6% among all the subjects sampled and 8.6% in HIV positive persons. The HIV rate in this study is twice the UNAIDS/WHO estimate for the country and twice the numbers of women than men were infected with HIV at a comparatively younger age, while males 55 years and over had higher HIV rates than those below 35. HCV and HIV/HCV coinfection was more commonly associated with males than females. This study showed that Hepatitis C serotype 2 is the most prevalent type in the country and was predominantly associated with HIV-1, and suggests that HCV serotype 2 spread earlier than serotypes 1 and 3. The mean CD4 count of apparently healthy males and females was 489/μl and 496/μl respectively, while the mean CD4 count at diagnosis (CD4dx) of HIV, and HIV/HCV persons was 310 cells/μl and 306 cells/μl respectively. Only about half of the apparently healthy population had CD4 counts of 500 cells and over (51 %), while 1.1 % (15/1377) had counts below 200 cells per microlitre for no explained reasons. HN/HCV co-infected person recorded a lower CD4 count at diagnosis than HIV alone infected persons and also a more significant decline in CD4+ than HIV infected alone persons. The study shows that high HIV rates were independent of the educational status of the individual, while history of sexually transmitted diseases, high income earning and involvements in polygamous marriages were all significant risk factors for HIV, HCV and HIV/HCV co-infection. Female circumcision, knowledge and use of condoms, blood oath, histories of blood transfusion and wife inheritance were not associated with HIV or HCV transmission. The study found an HIV incidence rate of 1.4% (4/288) during the 18 months follow-up period and identified Sexually Transmitted Diseases (STDs) as the associated risk factor. There is need for a new CD4+ staging in the country based on the population within the country and the initiation of a large scale longitudinal study to elucidate the risk factors associated with HCV in the country. The study has provided baseline data on CD4 and its trends in co-infected persons and also a baseline on the distribution and epidemiological pattern and associated risk factors of co-infection between HIV and HCV in the country. It has also determined the incidence of HIV and its associated risk factors in the country. The study has therefore contributed to our understanding of the natural history of these infections and provided an important frame work for possible intervention.
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Iwatani, Yasumasa. "Human Immunodeficiency Virus Type 1 Vpu modifies Cytopathic Effect through Augmented Virus Release." Kyoto University, 1997. http://hdl.handle.net/2433/202156.
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Matthews, James Robert. "Transcriptional activation of human immunodeficiency virus type 1 by NF-κb". Thesis, University of St Andrews, 1993. http://hdl.handle.net/10023/13981.
Повний текст джерелаАнотація:
This study has analysed some of the mechanisms involved in the transcriptional activation of the human immunodeficiency virus type 1 (HIV-1) by transcriptional modulator proteins of the NF-ĸB/rel family. Initial attempts to purify a single NF-ĸB (p50-p65) heterodimer species from HeLa cells suggested that a family of proteins might contribute to ĸB motif DNA binding activity. HeLa cell ĸB motif DNA binding proteins were shown to be modified by glycosylation. Using circularly permuted DNA probes carrying a KB motif, it was shown that ĸB binding proteins induced significant DNA bending upon binding, while studies of the effects of the poly amine spermidine on purified HeLa cell ĸB motif DNA binding proteins showed it greatly stimulated their DNA binding activity. The DNA binding activity of native ĸB motif DNA binding proteins was also greatly stimulated by the reducing agent dithiothreitol. Using a cDNA encoding the p105 precursor to the NF-ĸB p50 subunit, the wild type DNA binding and dimerisation region (aa35-381) of p50, and three cysteine to serine mutants at cysteine residues (aa62, 119, and 273) conserved throughout the NF-ĸB/rel/dorsal family, were expressed in bacteria. The dissociation constant of the aa62 p50 mutant for the ĸB motif was 10-fold higher than that of the wild type p50. Also, dissociation rate constants for the aa62 mutant-KB motif complex in both the presence and absence of spermidine were anomalously high. The above changes suggested a different DNA binding specificity for the aa62 mutant - this was confirmed by oligonucleotide competition studies. Oligonucleotide protection experiments suggested the presence of a cysteine residue in the p50 DNA binding site-substrate protection experiments showed that this was cysteine 62, and that this residue is involved in redox regulation of p50 DNA binding activity.
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Khalouei, Sam. "Translation initiation in human immunodeficiency virus type 1 (HIV-1)." Thesis, University of Ottawa (Canada), 2007. http://hdl.handle.net/10393/27866.
Повний текст джерелаАнотація:
Translation of human immunodeficiency virus type 1 (HIV-1) mRNAs is entirely dependent on the host translation machinery. There are two prevailing hypotheses regarding the translation initiation mechanism in HIV-1; conventional cap-dependent ribosomal scanning mechanism (CDRSM) and cap-independent entry of the ribosome, usually through an internal ribosome entry site (IRES). The first mechanism makes use of the Kozak consensus sequence in locating the translation initiation codon, similar to the mechanism observed in human mRNAs. Therefore, a thorough understanding of the Kozak consensus and translation initiation in human would also shed light on the mechanism of translation initiation in HIV-1. The role of Kozak +4G site in translation initiation has been controversial, with the alternative hypothesis explaining the prevalence of +4G by invoking the observation that small amino acids, coded by G-starting codons, which are efficient for N-terminal methionine excision (NME), are preferred at the penultimate (second) position. Using two bioinformatics approaches we provide strong support for this alternative hypothesis and provide evidence contradicting the involvement of +4G in translation initiation.
One of the predictions of the CDRSM hypothesis is a high conservation of Kozak consensus sequence in different HIV-1 sequences. Our results presented here validate this prediction. The CDRSM hypothesis also predicts that there should be a selective pressure against ATG usage in optimal context in the HIV-1 5'-UTR to avoid their erroneous detection by the scanning ribosome, whereas the IRES-dependent mechanism in the presence of stable secondary structures, predicts no such selective pressure because these ATGs would be embedded in the secondary structures. Here we demonstrate this selective pressure in the HIV-1 5'-UTR which further supports the CDRSM hypothesis. Finally, we present evidence for strong site conservation in the 5'-UTR of HIV-1 sequences, which not only point to as yet unknown mechanisms of translation initiation, but also provide a mean to separate HIV-1 and human mRNAs. This implies that it is theoretically possible to design HIV-1-specific translation inhibition drugs.
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Chambers, Anthony James St Vincent's Hospital UNSW. "The surgical management of patients with human immunodeficiency virus infection." Awarded by:University of New South Wales. St. Vincent's Hospital, 2001. http://handle.unsw.edu.au/1959.4/19367.
Повний текст джерелаАнотація:
Infection with the human immunodeficiency virus (HIV) is a major cause of morbidity and death globally, and the number of individuals infected with this virus is increasing in many nations. Advanced HIV infection causes immunocompromise that predisposes to opportunistic infections and malignancies that characterise the acquired immunodeficiency syndrome (AIDS). Although the management of many of these AIDS-associated infections and malignancies is by medical means, surgeons play an important role the diagnosis and management of many of these conditions. Furthermore, patients with HIV infection may present with surgical disorders or traumatic injuries that are not related to HIV or AIDS. Health care workers managing patients with HIV infection and AIDS, particularly those involved in performing invasive procedures, are at risk of exposure to this virus in infected blood and body fluids. St. Vincent's hospital, Sydney, is a teaching hospital and major treatment centre for patients with HIV infection and AIDS located in the inner-eastern suburbs of Sydney. Patients with HIV infection who underwent surgical procedures at St. Vincent's hospital during the period 1990 to 1999 were retrospectively reviewed in order to describe the nature of the operative procedures required in the management of these patients. There were 636 patients with documented infection with HIV who underwent 889 surgical procedures at St. Vincent's hospital during the period 1990 to 1999. The number of procedures performed for patients with known HIV infection was increasing during this period. Patients with HIV infection accounted for 1.1% of all surgical procedures performed at this institution during this period. The proportion of total operative cases that patients with known HIV infection represented was seen to be increasing during this period. Surgical procedures were performed during only a small proportion of admissions of patients with HIV infection to St. Vincent's hospital for this period (2.4% of these admissions). The patients were predominantly males in younger age groups. Anorectal procedures for the local treatment of benign conditions were the most common procedures performed for these patients, followed by procedures for the insertion or removal of long-term vascular access devices and other minor general surgical procedures. A large proportion of procedures were performed as day surgery cases (30%). Only a small proportion of cases were for the management of traumatic conditions (3%). A large proportion of patients with HIV infection (26%) underwent more than one procedure during this period, with anorectal disorders a common cause of repeat surgical admission. The operative findings after 498 surgical procedures performed for 360 patients with documented HIV infection during the period 1995 to 1999 were retrospectively reviewed. The number of cases in which AIDS-defining conditions were encountered were recorded, and varied according to the types of procedures performed. Overall, seventy AIDS-defining conditions were found at operation during sixty-five procedures (13% of all procedures for patients with HIV infection). Non-Hodgkin's lymphoma was the most frequently encountered AIDS-defining disorder found at operation, accounting for 41% of such conditions. Kaposi's sarcoma was the next most frequently encountered condition, accounting for 20% of cases followed by cytomegalovirus infection (11%). Procedures in which AIDS-defining conditions were commonly encountered included neurosurgical procedures (20 of 36 procedures were for AIDS-defining conditions), particularly stereotactic brain biopsy. Lymph node excision biopsies had AIDS-defining pathologies seen in 18 of 26 cases, particularly non-Hodgkin's lymphoma. AIDS-defining conditions were diagnosed in only 4% of anorectal procedures, with anal squamous cell malignant lesions a far more frequently observed disorder (diagnosed in 11% of cases). The clinical details of all patients who met the clinical criteria for AIDS who underwent midline laparotomy at St. Vincent's hospital during the period 1987 to 1998 were retrospectively examined. Thirty patients with AIDS underwent thirty laparotomies during this period. AIDS-defining conditions were found at fourteen procedures (47%). Non-Hodgkin's lymphoma was found in eleven of these laparotomies, Kaposi's sarcoma in two and cytomegalovirus in one. In nine of the patients with AIDS-defining conditions, the post-operative diagnosis was different to that expected pre-operatively. Patients with AIDS-defining conditions found at laparotomy had significantly lower serum albumin concentrations and body weight compared with those with more conventional surgical diagnoses. There was no difference in CD4 T-lymphocyte counts, the number of patients with a history of AIDS-defining conditions or the duration of HIV infection between these two groups. Patients with AIDS-defining conditions diagnosed at laparotomy required significantly longer post-operative hospital stays compared to those with other causes, although there was no difference in the incidence of post-operative complications or deaths occurring in these two groups. There was a high number of patients with post-operative complications seen after laparotomy (thirty-two complications in twenty-one patients; 70% of all patients). Chest infections, systemic sepsis and wound infections were the most frequently encountered post-operative complications. Five deaths occurred within thirty days of operation (17% of patients), and were due to overwhelming systemic sepsis in four cases and from blood loss and coagulopathy in one. The number and the nature of the complications and deaths occurring in patients with AIDS undergoing laparotomy at St. Vincent's hospital is in keeping with previously published reports from other centres. The clinical details of patients with documented HIV infection who underwent biliary tract procedures at St. Vincent's hospital during the period 1989 to 1998 were retrospectively reviewed. Eighteen patients with HIV (fourteen of which met the clinical criteria for AIDS) underwent cholecystectomy; ten for cholecystitis secondary to gallstones, one for mucocoele of the gallbladder due to obstruction of the cystic duct by a gallstone and seven for acalculous cholecystitis. Biliary tract procedures accounted for 24% of all abdominal procedures during this period. Patients were mostly male and in a relatively young age range. Cytomegalovirus infection was found in five cases of acalculous cholecystitis, Cryptosporidia in five and Microsporidia in two. A significantly greater proportion of patients with acalculous cholecystitis had a history of AIDS, and these patients had lower CD4 T-lymphocyte counts, compared with those patients with cholelithiasis. There was no statistical difference in the length of hospital admission or number of complications occurring in these two groups. Patients who had cholecystectomy performed as an elective procedure (n=7) were compared with those who had this procedure performed during admission for acute cholecystitis (n=11), and had a significantly lower duration of post-operative hospital stay. There was no difference in the number of complications occurring in these two groups. Laparoscopic cholecystectomy was performed in eight patients, and was not associated with a significant difference in hospital admission duration or incidence of complications when compared with the ten patients who underwent open cholecystectomy. The medical records of all patients presenting to St. Vincent's hospital during the period 1994 to 1998 with major penetrating wounds (gunshot wounds and stab wounds to the trunk or neck) were retrospectively examined to determine the number of such patients with a documented history of infection with HIV or hepatitis C virus (HCV), or with risk factors for these infections. Of the 148 patients with major penetrating wounds who were managed at St. Vincent??s hospital during this period, 5.4% had documented infection HCV and 1.3% with HIV. Risk factors were documented in thirty-one individuals (21%), with injecting drug use the most commonly recorded (19%). Individuals infected with HIV represent a substantial workload for surgical specialists at St. Vincent's hospital. Surgical procedures were an uncommon cause of admission for patients with HIV infection, but were important in the diagnosis and management of many AIDS-associated conditions and were increasing in number. AIDS-defining conditions accounted for only a small proportion of operative interventions in patients with HIV infection. Surgical procedures required in the management of patients with HIV infection encompassed a broad range of surgical specialties and types of procedures. AIDS-associated opportunistic infections and malignancy were frequently the cause of abdominal procedures in patients with HIV and AIDS. The number of patients with known HIV infection who present for elective and emergency surgical procedures, as well as the high prevalence of documented HIV and HCV in patients with major penetrating wounds at St. Vincent's hospital, reinforces the need for all health care workers to practice strict universal precautions against body fluid exposure at all times.
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Ma, Meihui. "Interactions of human immunodeficiency virus type 1 proteins with astrocytes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq23632.pdf.
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Belzile, Jean-Philippe. "Redirecting lentiviral integration : a study of human immunodeficiency virus integrase." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97906.
Повний текст джерелаАнотація:
Despite great advances in our understanding of the human immunodeficiency virus (HIV) life cycle, the mechanisms that underlie the progression of HIV from cellular entry of the viral core to stable integration of the provirus are poorly understood. Sites of integration of the HIV provirus are distributed along the full length of actively transcribed genes and appear to be determined through protein-protein interactions between the viral integrase and cellular proteins.Two cellular proteins have been proposed to perform integration targeting roles, the chromatin-remodeling factor integrase interactor 1 (INI1/hSNF5/BAF47) and the lens epithelium-derived growth factor/transcriptional co-activator (LEDGF). Here, we report the initiation of two novel integration assays to study the contribution of INI1 and LEDGF in target site selection. Elucidating these molecular determinants and their functional implications is also of particular interest to anti-HIV therapy and could have major impact on the safety of gene therapy protocols.
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D'Addario, Mario G. Jr. "Cytokine gene expression in human immunodeficiency virus infected myeloid cells." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=56776.
Повний текст джерелаАнотація:
Results indicate that U9-IIIB and PLB-IIIB cells stimulated with PMA, LPS or recombinant cytokines transcribed and translated significantly higher levels of TNF-$ alpha$, IL-1$ alpha$, IFN-$ alpha$, IL-1$ beta$, and IFN-$ beta$. Furthermore it appears that HIV infection of PLB-985 cells induces monocytic differentiation and alterations in the binding of NF-$ kappa$B related proteins. PLB-IIIB cells demonstrated characteristics reflecting differentiation including morphological alterations, changes in c-fms and c-myc proto-oncogene expression, and increased expression of CD14 cell surface antigen. Examination of the IL-1$ beta$ promoter revealed a DNA sequence capable of interacting with the NF-$ kappa$B family of proteins; oligonucleotides containing 1-3 copies of this IL-1$ beta$-$ kappa$B sequence were synthesized and shown to bind NF-$ kappa$B proteins from LPS and PMA treated U937 and U9-IIIB cells. Recombinant NF-$ kappa$B protein subunits specifically bound monomeric and dimeric copies of this IL-1$ beta$-$ kappa$B sequence and binding was eliminated by competition with unlabeled wild type but not mutant oligonucleotides. Results indicate that IL-1$ beta$ gene expression may be significantly elevated in HIV infected cells and that transcriptional regulation by NF-$ kappa rm B /{ it rel /}$ proteins may mediate its activation.
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Milev, Miroslav. "Characterizing the staufen 1 human immunodeficiency virus type 1 ribonucleoprotein." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=96998.
Повний текст джерелаАнотація:
Human Immunodeficiency Virus type 1 (HIV-1) is a member of the Retrovirus family and is the causative agent of Acquired Immunodeficiency Syndrome (AIDS). As an obligate intracellular parasite, HIV-1 uses cellular proteins and machinery to ensure transmission to uninfected cells. One such cellular protein involved in the late stages of viral replication is Staufen1. It is a main component of mRNA ribonucleoproteins (RNPs) and plays distinct roles in mRNA transport, translation and decay. In the context of HIV-1, Staufen1 was initially found to be selectively encapsidated into the virions. Subsequent work determined its association with vRNA and precursor protein Gag within HIV-1 RNPs. Recently we demonstrated that Staufen1 regulates the viral assembly process by inducing Gag multimerization.In Chapter 2 of the present work, we used tandem affinity purification method followed by mass spectrometry to characterize the Staufen1-containing RNPs. We focused on the investigation of the proteins that associate with Staufen1 complexes, isolated from cells that either do or do not express HIV-1. We further performed a detailed comparison of the protein content between native Staufen1 and Staufen1 HIV-1 RNPs and defined the modulations caused from HIV-1 expression. In Chapter 3, we used bimolecular and trimolecular fluorescence complementation methods (BiFC and TriFC) that allow for direct visualization and localization of protein-protein and protein-protein and RNA interactions in living cells, to show that Gag and Staufen1 interact, which was demonstrated by small multi-fluorescent punctae or vesicles in cells. We demonstrated that these protein partners mainly associate in the cytoplasm. However, we also found that they interact at cholesterol-enriched GM-1-containing membrane microdomains. Importantly, Gag specifically recruited Staufen1 to these lipid raft membranes suggesting a key function for this host factor during Gag assembly. Notably in TriFC experiments, in which one protein partner was tethered to mRNA, Gag-Staufen1 interactions were observed demonstrating active recruitment of one protein when the other is bound to mRNA.Overall, we used both proteomics and live cell visualization to examine fundamental viral-host interactions. We have completely characterized the composition of Staufen1 RNPs and have demonstrated how HIV-1 uses these RNPs for its own purpose. These studies also enhance our understanding of the mechanisms and the specific dynamic features of the viral-host (Gag-Staufen1) interactions in living cells, as monitored by the modern fluorescence complementation assays. The findings presented here are significant help to advance research in the HIV-1 field because a better understanding of the mechanism of retrovirus assembly and budding will aid in the development of novel antiviral therapies targeting the critical late steps in the viral replication cycle.Le virus d'immunodéficience humaine de type 1 (VIH-1) est un membre de la famille de Rétrovirus et est responsable du syndrome d'immunodéficience acquise (SIDA). Considéré comme un parasite intracellulaire obligatoire, le VIH-1 utilise les protéines et les machineries cellulaires pour assurer la transmission aux cellules non infectées. Un des facteurs impliqués dans les étapes finales de réplication virale est la protéine Staufen1. Cette protéine est un composant important des ARNm ribonucléoprotéiques et joue des rôles clés dans le transport, la traduction et la dégradation de l'ARNm. Concernant le VIH-1, Staufen1 a été initialement découvert comme étant spécifiquement encapsidé dans les virions. Des travaux plus approfondis ont déterminé son association avec l'ARNv et le précurseur Gag dans les VIH-1 RNPs. Récemment, nous avons démontré que Staufen1 régule le processus d'assemblage viral en induisant le multimérisation de Gag.Dans le travail présent, nous avons employé la méthode de purification d'affinité en tandem suivie de la spectrométrie de masse pour caractériser les RNPs contenus dans Staufen1. Nous nous sommes concentrés sur la recherche des protéines qui s'associent aux complexes Staufen1 isolés des cellules qui expriment ou non VIH-1. Ensuite, nous avons effectué une comparaison détaillée du contenu protéique entre Staufen1 sous forme native et Staufen1 complexé au RNPs VIH-1 et nous avons défini les modulations causées par l'expression de VIH-1.Nous avons utilisé les méthodes de complémentation par fluorescence bimoléculaire et trimoleculaire qui permettent la visualisation et la localisation directes des interactions protéine-protéine et des interactions protéine-protéine et d'ARN dans des cellules vivantes, pour prouver que Gag et Staufen1 interagissent comme démontré par la fluorescence ponctuée ou les vésicules dans les cellules. Nous avons démontré que les protéines partenaires s'associent principalement dans le cytoplasme. Cependant, nous avons également constaté qu'ils interagissent dans des microdomaines membranaires contenant du cholestérol enrichis en GM-1. De manière importante, Gag recrute spécifiquement Staufen1 au niveau de ces membranes de radeaux lipidiques, suggérant une fonction essentielle de ce facteur d'hôte pendant l'assemblage de Gag. En particulier, des expériences de TriFC dans lesquelles une protéine partenaire est attachée à l'ARNm ont permis de montrer des interactions Gag-Staufen1 indiquant un recrutement actif des protéines lorsqu'elles sont attachées à l'ARNm.De façon générale, les travaux présentent des recherches de protéomique fondamentale et de visualisation de cellules vivantes d'interaction virus-hôte. Ces expériences présentent la caractérisation complète de la composition de Staufen1 RNPs et démontre comment le VIH-1 s'adapte pour ses propres besoins. Cette thèse s'enrichit également de notre compréhension des mécanismes et des caractéristiques dynamiques spécifiques des interactions virus- hôte (Gag-Staufen1) dans des cellules vivantes, contrôlées par des techniques récentes de complémentation de fluorescence. Les résultats présentés ici sont considérables et contribuent à l'avancée des recherches dans le domaine du VIH-1, parce qu'une meilleure compréhension du mécanisme de l'ensemblage et du bourgeonnement du rétrovirus augmente la possibilité de développer de nouvelles thérapies antivirales, visant les étapes tardives critiques du cycle viral de réplication.
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Goulder, Philip J. R. "Escape of human immunodeficiency virus from the cellular immune response." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.339291.
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Baird, Heather A. "Mechanisms of Intersubtype Recombination of Human Immunodeficiency Virus Type One." Case Western Reserve University School of Graduate Studies / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=case1120599751.
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Watson, Victoria. "The clinical pharmacology of Human Immunodeficiency Virus (HIV) therapy failure." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/18853/.
Повний текст джерелаАнотація:
The work in my thesis focuses on developing highly sensitive tests, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the measurement of antiretroviral drugs within plasma, cells, and cerebral spinal fluid from clinical studies evaluating compartmentalised antiretroviral therapy (ART) pharmacokinetics and forgiveness for missed or late dosing. Firstly I developed and validated a LC-MS/MS assay to quantify the antiretroviral (ARV) drugs, lopinavir, darunavir, ritonavir and raltegravir in peripheral blood mononuclear cells (PBMCs). This intracellular assay included optimising methodology for cell separation to minimise loss of drug (Chapter 4). All drugs eluted within an 8 minute run time. Matrix effects were minimal (-2.9%). Calibration curves were validated over a concentration range of 0.4-150ng/mL. Intra and inter assay variation ranged between 0.01-2.29% for precision and 96.76-102.32% for accuracy. Secondly I developed and validated a LC-MS/MS assay to simultaneously detect and quantify 10 ARVs; maraviroc (MVC), nevirapine (NVP), rilpivirine (RPV), raltegravir (RAL), atazanavir (ATV), darunavir (DRV), amprenavir (APV), ritonavir (RTV), lopinavir (LPV) and etravirine (ETV) in cerebral spinal fluid (CSF). All drugs eluted within a 10 minute run time. Calibration curves were validated over the following concentration ranges; LPV, MVC, RTV = 0.78-100 ng/mL, RAL, APV, ATV, RPV, ETV, DRV = 1.95-250 ng/mL and NVP = 19.5-2500 ng/mL (r2 values >0.99; quadratic 1/x). Intra and inter assay variation ranged between 1.59-15% for precision and -10.5-6.4% for accuracy. Carryover was <20% of the lower limit of quantification for all drugs. The recovery was >70% and the CV% at low, medium and high concentrations was less than 20% for all drugs. Thirdly I developed and validated a LC-MS/MS assay to quantify intracellular tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) within PBMCs. This work was very technically challenging and something that was not being done by any other laboratory within the United Kingdom. Analytes eluted within 12 minutes run-time with adequate separation. Calibration curves were validated over the following range TFV-DP=0.35-10.91 ng/mL, FTC-TP=0.38-103.17 ng/mL (r2 values >0.99; linear 1/x). The lower limit of quantification was <20 %, signal to noise was >5% and carryover <0.1%. The precision was; TFV-DP=6.3-11% and FTC-TP=6-18.6%, and accuracy was TFV-DP=97.5-100.8%, FTC-TP=98-100.3%. Finally, all assays developed and validated were successfully applied to collaborative clinical trials (see Communications; Published Research Papers). Benefits are expected to accrue from this work in the design of more forgiving therapy regimens for HIV patients, and better drug selection to specifically target HIV replicating within sanctuary sites.
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Motohara, Makiko. "Influence on thymopoiesis of simian and human immunodeficiency virus infection." Kyoto University, 2007. http://hdl.handle.net/2433/136437.
Повний текст джерелаАнотація:
Kyoto University (京都大学)0048
新制・課程博士
博士(人間・環境学)
甲第13166号
人博第373号
新制||人||91(附属図書館)
18||D||174(吉田南総合図書館)
UT51-2007-H439
京都大学大学院人間・環境学研究科相関環境学
(主査)教授 小松 賢志, 助教授 倉橋 和義, 助教授 三浦 智行
学位規則第4条第1項該当
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Anderson, Jon Paul. "Molecular diversity and evolution of human immunodeficiency virus type 1 /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/8049.
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Clark, W. Andrew, and Eileen M. Cress. "Nutritional Issues and Positive Living in Human Immunodeficiency Virus/AIDS." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/2495.
Повний текст джерелаАнотація:
Key Points: (1) Nutrition management for individuals infected with HIV can be helpful in maintaining lean body weight, combating oxidative stress, reducing complications from hyperglycemia and hyperlipidemia, and managing gastrointestinal function. (2) Patients may need to be individualized to meet each individual's unique requirements. (3) Consideration should be given to including the expertise of a registered dietitian/nutritionist s part of the health care team to promote wellness in the individuals infected with HIV.
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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.
Повний текст джерелаАнотація:
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).
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Simmonds, Peter. "Detection of antibody responses to infection with herpes simplex virus and human immunodeficiency virus." Thesis, University of Edinburgh, 1988. http://hdl.handle.net/1842/26933.
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Alimohammadi, Azin. "An investigation of susceptibility of alveolar macrophages to HIV 1 infection." Thesis, Imperial College London, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289878.
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Schockmel, Gerard Alphonse. "Construction of a binding site for HIV-1 GP120 in rat CD4." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302857.
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Agranoff, Daniel David. "Cation transporters of mycobacterium tuberculosis." Thesis, St George's, University of London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249372.
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