The causative agent of AIDS (acquired immune deficiency syndrome), HIV (human immunodeficiency virus), is one of the most extensively studied pathogens in modern history. The virus has multiple mechanisms of persisting in the host including evading host immune response. Since HIV-1 depends heavily on the host machinery for various aspects of its life cycle, unraveling the complex interplay between the host and HIV-1 could provide new clues to therapeutic avenues. In T cells, HIV assembles and subsequently buds through the plasma membrane incorporating host derived proteins and lipids in the viral envelope. HIV is thought to utilize a pre-existing mechanism for the budding of normal cellular vesicles called microvesicles to exit host cells. The evidence for this theory comes from reports of similarities between HIV and microvesicles observed for a small subset of proteins and lipids, leading to controversies about its validity. To further test this hypothesis, we utilized lectin microarrays to obtain a comprehensive glycomic profile of HIV and microvesicles derived from a panel of T cell lines. Glycosylation is critical to protein sorting and has a crucial role in HIV-1 biology, making it an ideal marker to compare the particles and the host cell membrane. We observed similar glycomic profiles for HIV-1 and microvesicles strongly suggesting an analogous mode of egress. Glycosylation of both particles seems to vary based on the parent cell line, providing additional evidence for this hypothesis. Microvesicles are involved in immune response modulation; hence the incorporation of microvesicular proteins could influence interactions of HIV with the immune system. The differences in glycosylation between these two particles could be potentially explained by the heavily glycosylated viral envelope glycoprotein. I also demonstrated that these vesicles bud from particular glycan enriched domains of the plasma membrane. Additionally, this work sheds light on the potential mode of interaction between galectin, an immune lectin and HIV-1. This work strongly argues for a conserved mechanism of exocytosis for both particles and sets the stage for examining the role of glycosylation in trafficking of proteins to the sites of microvesicular and viral budding. / text

published_or_final_version / Microbiology / Master / Master of Philosophy

Background: Sexually transmitted diseases (STD) remain a public health concern in worldwide. Human immunodeficiency virus (HIV), one of the STDs, is associated with the increase risk of other STD infections. According to Centers for Disease Control and Prevention (CDC), individuals who are infected with STDs are more likely to be infected with HIV than uninfected individuals. As HIV and other STDs share the same transmission route, the co-infection may be observed more frequently in the population. To control the number of co-infection, screening programs are essential in all areas. While screening for individual infections are necessary, the prevalence of co-infection should also be evaluated for surveillance programs. The prevalence of individual STDs have been studied in various reviews, but the population prevalence of the co-infection was not widely studied. Therefore, a systematic review is conducted to provide a summary of the prevalence of HIV with syphilis, chlamydia, gonorrhea and herpes simplex virus (HSV-2) and co-infection in various populations. Methods: PubMed database is chosen for selection of potential publications in this systematic review. Various keywords are used for the search and and only English publications are selected for review. Studies with statistical data on individual infection but not the co-infection were excluded. Results: Ten studies from various populations are selected for this review. Nine studies were conducted in healthcare facilities and one was conducted in a working site. The number of study participants ranged from 336 to 1661 with a mean age of 32 years old. The average of prevalence of HIV and the chosen STDs was around 20%—highest prevalence is observed in HSV-2 with HIV co-infection. Conclusion: The prevalence of co-infection is low but it cannot be neglected. Simultaneous screening for HIV and other STDs is not necessary in all areas, but it will be very useful in certain facilities where high-risk populations, for example sex workers, MSM etc are served. Such low prevalence of STD co-infection should be maintained and it is the responsibility of both the individuals and the society. / published_or_final_version / Public Health / Master / Master of Public Health

Acquired immunodeficiency syndrome (AIDS) remains an epidemic illness with no known cure. Survival time after infection with the human immunodeficiency virus (HIV), has been lengthened considerably. Rates of new infection among the at-risk male homosexual populations have decreased. Prevention is possible through effective, targeted interventions. This study is an exploration of the role or health locus of control, an individual difference construct from the area of social learning theory, in the maintenance of health-oriented behaviours, co-risk indicative behaviours, and high-risk behaviours in a population of adult male homosexuals attending a general medical clinic. The findings result in distinctly different past histories and present patterns of homosexual behaviours among the two serostatus subpopulations. Low internal expectancy of control over health repeatedly relates in distinctive patterns with the areas of level of happiness, condom usage, and hish-risk sexual behaviours. High internal expectancy of control relates significantly to knowledge-related variables. The physician plays a pivotal role as the source of useful information in this at-risk population. The study population as a whole reports accurate knowledge about HIV and AIDS. The men have reduced high-risk behaviours, increased safer sexual behaviours, and implemented the changes advocated. Serostatus differentiates for many high-risk behavioural patterns. There remains a small core of men among the study participants who continue to participate in high-risk sexual behaviours.

Human immunodeficiency virus (HIV) infection is a worldwide epidemic where infected individuals usually develop acquired immunodeficiency syndrome (AIDS). HIV is primarily spread by sexual transmission across mucosal tissue where dendritic cells (DC) reside. DC regulate immune responses through their unique ability to capture antigen, migrate to lymphoid tissue, and activate naive T cells. In this Thesis, we have investigated whether HIV influences the migration of DC, thereby influencing their capacity to regulate immune function and facilitate transport of HIV to T cell rich lymphoid tissue. Transmigration assays demonstrated that the predominant HIV strain during primary infection, R5 HIV-1, was chemotactic for immature DC (iDC). Addition of soluble CD4 enhanced iDC migration to R5 HIV, presumably by binding to R5 HIV and altering the conformation to enhance binding to CCR5. Our results suggested that iDC migrated specifically to R5 and not X4 HIV gp120, through interactions between the extracellular loop-2 (ECL-2) domain of CCR5 with the V3 loop region of R5 gp120. iDC prepared from HIV-infected subjects were shown to have impaired chemotaxis to inflammatory chemokines compared with iDC from healthy individuals. Furthermore, the level of inhibition appeared to be proportional to the severity of disease progression in HIV infected subjects. Interestingly, chemotaxis of iDC from long-term non-progressor individuals was similar to normal individuals, whereas migration of iDC from typical progressors was greatly impaired. These differences did not appear to be related to the level of CCR5 expression or patient viral load. The protease inhibitor Indinavir used in antiretroviral therapy, limited DC trans-endothelial migration to chemokines, reduced DC-SIGN expression and increased CD83 on iDC. The results suggested that Indinavir inhibited proteases necessary for DC migration by adversely affecting interactions between DC-SIGN, VLA-4 and VLA-5 and ligands on the endothelium and underlying fibronectin matrix. A novel method has been successfully developed for amplifying rare HIV-specific CDS cells using DC transfected with HLA antigens matching HIV-infected subjects. This has enabled us to amplify HIV-specific CDS T cells by 10- to 60-fold. This may help us to clone and characterise HIV-specific CDS T cells from highly exposed persistently seronegative (HEPS) individuals. In summary, the results in this Thesis demonstrate that R5 HIV mimics chemokines to subvert the natural trafficking of DC. Indeed, we have shown that DC from typical progressors have severely impaired migration. This may have serious consequences on DC immunoregulation, compromising the immune function of these infected individuals.

HIV-positive men face multiple challenges when deciding whether or not to disclose their serostatus to sex partners. This survey design using repeated measures examined disclosure of HIV-positive serostatus to sex partners in an ethnically diverse population of men (N= 93) recruited from the community in O'ahu, Hawai'i. The framework guiding the research was Social Cognitive Theory (Bandura, 1987), with a specific focus on self-efficacy for disclosure decision-making and for negotiating safe sex. The aims of the research were to: 1) describe HIV serostatus disclosure to sex partners; 2) describe self-efficacy for disclosure to sex partners and self-efficacy for negotiating safer sex; 3) determine the relationships between demographic, HIV-illness, drug use history, self-efficacy and sex partner variables (relationship status, serostatus), and self-disclosure, and; 4) determine the relationships between demographic, HIV-illness, drug use history, self-efficacy, sex partner variables, self-disclosure, and condom use by the men in the sample. A convenience sample of HIV-seropositive men was enlisted through both active outreach and passive recruitment (posters and public advertisement). Survey responses were anonymous, as the subject matter being asked was sensitive in nature. Results reveal that self-disclosure to sex partners varied based on sex partner serostatus and relationship status, and was significantly influenced by perceived self-efficacy, by income, education, years since diagnosis and contextual factors including cocaine use before sex. Subjects were least likely to disclose to a sex partner whose serostatus was not discussed. An unknown partner serostatus was also significantly associated with less disclosure. The more committed the relationship, the greater the likelihood that a subject would self­ disclose. The longer the time since initial HIV diagnosis the more likely a subject was to disclose to sex partners. High self-efficacy scores were associated with self-disclosure, and with condom use. Cocaine use before sex was associated with less disclosure and less condom use. Self-disclosure was significantly associated with condom use as well. Although a causal relationship is not implied, self-disclosure practices did influence safe sex behavior. Implications for nursing and for future research are discussed.

Copy of author's previously published article on back end-paper. / Bibliography: leaves 105-158. / xii, 160, [58] leaves, [35] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Studies the early events in the synthesis of HIV RNA and integration if viral DNA using a cell-to-cell transmission of infection model. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology & Immunology, 1998

Dissertation (Ph.D.) -- The Institute for Clinical Social Work, 2007. / A dissertation submitted to the faculty of the Institute of Clinical Social Work in partial fulfillment for the degree of Doctor of Philosophy.

Thesis (M.S.)--Villanova University, 2008. / Psychology Dept. Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.