Digital Commons Network^™

Simian Immunodeficiency Virus-Infected Rhesus Macaques With Aids Co-Develop Cardiovascular Pathology And Encephalitis, Kevin S. White, Joshua A. Walker, John Wang, Patrick Autissier, Andrew D. Miller, Nadia N. Abuelezan, Rachel Burrack, Qingsheng Li, Woong-Ki Kim, Kenneth C. Williams

Nebraska Center for Virology: Faculty Publications

Despite effective antiretroviral therapy, HIV co-morbidities remain where central nervous system (CNS) neurocognitive disorders and cardiovascular disease (CVD)-pathology that are linked with myeloid activation are most prevalent. Comorbidities such as neurocogntive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. We sought to investigate if cardiac pathology (inflammation, fibrosis, cardiomyocyte damage) and CNS pathology (encephalitis) develop together during simian immunodeficiency virus (SIV) infection and if their co-development is linked with monocyte/ macrophage activation. We used a cohort of SIV-infected rhesus macaques with rapid AIDS and demonstrated that SIV encephalitis (SIVE) and CVD pathology occur together more frequently …

Changes In Rna Expression Of Hut78 Cells Resulting From The Hiv-1 Viral Protein R R77q Mutation, Joshua S. Ramsey

Theses and Dissertations

Human immunodeficiency virus type 1 (HIV-1) is the causative virus for acquired immunodeficiency syndrome (AIDS). AIDS is characterized by chronic inflammation and reduction of CD4+ T-cells in the blood. This leads to the patient becoming immunocompromised and much more susceptible to disease in general. Different phenotypes in the progression of AIDS have been observed in patients in either progressing to AIDS faster as a Rapid Progressor (RP), or slower as a Long-Term Non-Progressor (LTNP). Researching elements that result in the LTNP phenotype is of interest as it has the potential to offer alternative treatments and therapies to those suffering from …

Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista

Selected Honors Theses

Cyclopropyl acetylene (CA) is a key intermediate in the synthesis of the human immunodeficiency virus (HIV) reverse transcriptase inhibitor, Efavirenz (EFV), an antiviral drug used to treat HIV. CA is an expensive raw material, difficult to obtain, and employed in the preparation of medications to combat acquired immunodeficiency syndrome (AIDS). It was found that the structure could be synthesized by the utilization of PCl5; however, this resulted in unwanted ring opening products. To address this issue, a one pot synthesis was developed using Ph3PCl2 as a mild chlorinating agent. In addition, a new analog has been proposed substituting the cyclopropyl …

Analysis Of The Cytopathogenic Effect Of Different Hiv-1 Vpr Isoforms On Primary Human Cd4+ T Cells And A Model Cell Line, Jonatan Josue Fierro Nieves

Theses and Dissertations

Human Immunodeficiency Virus (HIV) is the causal agent of acquired immunodeficiency syndrome (AIDS), a disease characterized by the depletion of CD4+ T cells which impairs immune response. Analysis of HIV-1 infected patients has identified two distinctive phenotypes that differ in length of time towards the development of AIDS, Rapid Progressor (RP) and Long-Term Non-Progressor (LTNP) patients. The cause of the differences between these two groups is a process that is still under investigation. Hints about a possible cause have been attributed to the discovery of mutations in the viral protein R (Vpr) that have been associated with these phenotypes: mutations …

From The Headlines: A Textual Analysis Of Social Polarization And Discord In Times Of Pandemic Across A Century In The United States, Alexa Demarco

Undergraduate Honors Theses

Within the past century, three major pandemics have affected the United States – the Spanish Flu, AIDS, and COVID-19. Each of these pandemics has tested the capabilities of the public health sector and the social resilience of the population. Scientists have studied the viruses and implemented public health measures to limit viral transmission, but the social responses to these preventative measures proved to be difficult to predict and control. The dissonance and polarization between the public health initiatives and the response of the general public in the most recent pandemic was apparent. Was this a pattern in other pandemics? Was …

The Effects Of Polymorphisms Of Viral Protein R Of Hiv-1 On The Induction Of Apoptosis In Primary Cells And The Characterization Of Twelve Novel Bacillus Anthracis Bacteriophage, Jacob D. Fairholm

Theses and Dissertations

Viral protein r (Vpr) of Human immunodeficiency virus type 1 (HIV-1) plays an important role in the ability of the virus to infect cells and cause disease. Two polymorphisms to Vpr have been shown to result in differences in disease progression in infected individuals. R36W tends to result in rapid disease progression while R77Q results in long-term non-progression. In order to better understand how these polymorphisms result in these different disease phenotypes, our lab has recently shown that in cell culture, the R36W polymorphism results in increased viral replication and greater induction of cell death. On the other hand, infection …

Genome-Wide Association Study Reveals Genetic Variants Associated With Hiv-1c Infection In A Botswana Study Population, Andrey Shevchenko, Daria V. Zhernakova, Sergey Malov, Aleksey Komissarov, Sofia Kolchanova, Gaik Tamazian, Alexey Antonik, Nikolay Cherkasov, Sergey Kliver, Anastasiia Turenko, Mikhail Rotkevich, Igor Evsyukov, David Vlahov, Prisca K. Thami, Simani Gaseitsiwe, Vladimir Novitsky, Myron Essex, Stephen James O'Brien

Biology Faculty Articles

Although there have been many studies of gene variant association with different stages of HIV/AIDS progression in United States and European cohorts, few gene-association studies have assessed genic determinants in sub-Saharan African populations, which have the highest density of HIV infections worldwide. We carried out genome-wide association studies on 766 study participants at risk for HIV-1 subtype C (HIV-1C) infection in Botswana. Three gene associations (AP3B1, PTPRA, and NEO1) were shown to have significant association with HIV-1C acquisition. Each gene association was replicated within Botswana or in the United States–African American or United States–European American AIDS …

Bispecific Anti-Hiv Immunoadhesins That Bind Gp120 And Gp41 Have Broad And Potent Hiv-Neutralizing Activity, Seth H. Pincus, Ryan B. Craig, Lauren Weachter, Celia C. Labranche, Rafiq Nabi, Connie Watt, Mark Raymond, Tami Peters, Kejing Song, Grace A. Maresh, David C. Montefiori, Pamela A. Kozlowski

School of Graduate Studies Faculty Publications

We have constructed bispecific immunoglobulin-like immunoadhesins that bind to both the HIV-envelope glycoproteins: gp120 and gp41. These immunoadhesins have N terminal domains of human CD4 engrafted onto the N-terminus of the heavy chain of human anti-gp41 mAb 7B2. Binding of these constructs to recombinant Env and their antiviral activities were compared to that of the parental mAbs and CD4, as well as to control mAbs. The CD4/7B2 constructs bind to both gp41 and gp140, as well as to native Env expressed on the surface of infected cells. These constructs deliver cytotoxic immunoconjugates to HIV-infected cells, but not as well as …

Oral Vaccination Approaches For Anti-Shiv Immunity, Erandi Velarde De La Cruz, Lingyun Wang, Deepanwita Bose, Sailaja Gangadhara, Robert L. Wilson, Rama R. Amara, Pamela A. Kozlowski, Anna Aldovini

School of Graduate Studies Faculty Publications

We modified a Sabin Oral Poliovirus Vaccine (OPV) vector to permit secretion of the antigens of interest with the goal of improving anti-HIV Env humoral responses in a SHIV mucosal immunization composed of DNA and recombinant OPVs. We evaluated stimulation of systemic and mucosal cell-mediated and humoral immunity in Rhesus macaques by two regimens, both involving a prime with a SHIVBG505 DNA construct producing non-infectious particles formulated in lipid nanoparticles, administered in the oral cavity, and two different viral vector boostings, administered in the oral cavity and intestinally. Group 1 was boosted with rMVA-SHIVBG505, expressing SIV Gag/Pol and HIVBG505 Env. …

Sequence-Independent Assay For Hiv Viral Load Quantitation, Omar El Merhebi

Honors Undergraduate Theses

Although nucleic acid tests (NATs) for human immunodeficiency virus (HIV) exhibit many advantages, such as early detection and viral load quantification, over immunological assays, their widespread use is limited by their demand for high-level infrastructure, sophisticated equipment, and advanced staff competence. Furthermore, when quantifying viral loads of patients, it has been reported that these assays can underestimate viral quantities by 22- to 100-fold due to primer-template mismatches in more divergent HIV subtypes. Therefore, we have developed a cost-effective and sequence-independent assay for the detection and quantification of HIV utilizing a modified nucleic acid sequence-based amplification (NASBA) protocol coupled to an …

Methods To Identify And Develop Drugs For Cryptosporidiosis, Rajiv Satish Jumani

Graduate College Dissertations and Theses

Cryptosporidiosis is a common diarrheal disease caused by intestinal infection with the apicomplexan parasite Cryptosporidium, in humans usually either with C. hominis or C. parvum. Unfortunately, given a large burden of disease in children and immunocompromised people like AIDS patients, the only currently approved treatment, nitazoxanide, is unreliable for these patient populations. To address the urgent need for new drugs for the most vulnerable populations, large phenotypic screening efforts have been established to identify anti-Cryptosporidium growth inhibitors in vitro (hits). However, in the absence of a gold standard drug, the in vitro and in vivo characteristics that should be used …

The Impact Of African American Male Incarceration Rates On The Racial Disparities In Hiv/Aids Rates, Michelle S. Aelion

DePaul Discoveries

In the United States, HIV/AIDS disproportionately impacts African Americans and African American communities. The nature of this national health disparity is complex and cannot be explained simply by one factor or an individual’s behavior within a given community. This paper suggests that the disparity in African American male incarceration rates is among the most important factors to consider in the racial disparities of HIV/AIDS rates. Existing studies on relevant subjects were examined and used to create a conceptual model of factors. This model presents an outline of factors during pre-incarceration, incarceration, and post-incarceration that contribute to the racial disparities in …

An Assessment Of The Role Of Chimpanzees In Aids Vaccine Research, Jarrod Bailey

Jarrod Bailey, PhD

Prior to Simian Immunodeficiency Virus (SIV)-infected macaques becoming the ‘model of choice’ in the 1990s, chimpanzees were widely used in AIDS vaccine research and testing. Faced with the continued failure to develop an effective human vaccine, some scientists are calling for a return to their widespread use. To assess the past and potential future contribution of chimpanzees to AIDS vaccine development, databases and published literature were systematically searched to compare the results of AIDS vaccine trials in chimpanzees with those of human clinical trials, and to determine whether the chimpanzee trials were predictive of the human response. Protective and/or therapeutic …

Human Herpesvirus 6a Infection And Immunopathogenesis In Humanized Rag2-/-Γc-/- Mice And Relevance To Hiv/Aids And Autoimmunity, Anne Tanner

Theses and Dissertations

Human herpesvirus 6A (HHV-6A) has yet to be definitively linked to a specific disease. This is due in part to the ubiquitous nature of the virus. Humanized Rag2^-/-γc-/- (Rag-hu) mice were tested to determine if these were a suitable animal model to study the virus. Both cell-free and cell-associated virus was used for infection and both were found to be efficient at infecting the mice. Viral DNA was found in the plasma and cellular blood fractions, bone marrow, lymph node, and thymus, indicating successful infection and propagation of the virus in vivo. The CD3+CD4- population was depleted, while the …

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …

The Association Between Vitamin A Status Or Supplementation And Hiv/Aids, Mikaela Kathleen Curtis

Food Science and Nutrition

The human immunodeficiency virus (HIV) has infected millions of people since the start of the epidemic in the early 1980s. HIV is the etiologic agent of the acquired immunodeficiency syndrome (AIDS), which has taken millions of lives. It is extremely difficult for particular populations to receive medication to treat HIV infection and prevent the progression of HIV to AIDS. Multiple studies have examined the effect of vitamin A on HIV infection, due to its immune stimulating effects. It is unclear whether an association exists between vitamin A and different aspects of HIV. This review examined the effect of vitamin A …

In Search Of Safety, Negotiating Everyday Forms Of Risk: Sex Work, Criminalization, And Hiv/Aids In The Slums Of Kampala, Serena Cruz

FIU Electronic Theses and Dissertations

This dissertation offers an in-depth descriptive account of how women manage daily risks associated with sex work, criminalization, and HIV/AIDS. Primary data collection took place within two slums in Kampala, Uganda over the course of fourteen months. The emphasis was on ethnographic methodologies involving participant observation and informal and unstructured interviewing. Insights then informed document analysis of international and national policies concerning HIV prevention and treatment strategies in the context of Uganda. The dissertation finds social networks and social capital provide the basis for community formation in the sex trade. It holds that these interpersonal processes are necessary components for …

An Almost Ideal Demand System Analysis Of Orange And Grapefruit Beverage Consumption In The United States, Catrice Taylor

All Theses

This thesis estimates a demand system for natural fruit juices and flavored citrus drinks. Consumption and price data from the Florida Department of Citrus is used to estimate a Linear Approximate Almost Ideal Demand System for natural fruit and fruit juice drink elasticities. The monthly data covers the period from October 2004 to June 2014. Elasticities show orange juice does not have a substitute among the other beverages. 100% orange juice and grapefruit juice are compliments, although other studies have found them to be substitutes.

Gwatch: A Web Platform For Automated Gene Association Discovery Analysis, Anton Svitin, Sergey Malov, Nikolay Cherkasov, Paul Geerts, Mikhail Rotkevich, Pavel Dobrynin, Andrey Shevchenko, Li Guan, Jennifer L. Troyer, Sher L. Hendrickson, Holli Hutcheson Dilks, T. K. Oleksyk, Sharyne Donfield, Edward Gomperts, Douglas A. Jabs, Efe Sezgin, Mark Van Natta, P. Richard Harrigan, Zabrina L. Brumme, Stephen J. O'Brien

Biology Faculty Articles

Background: As genome-wide sequence analyses for complex human disease determinants are expanding, it is increasingly necessary to develop strategies to promote discovery and validation of potential disease-gene associations.

Findings: Here we present a dynamic web-based platform – GWATCH – that automates and facilitates four steps in genetic epidemiological discovery: 1) Rapid gene association search and discovery analysis of large genome-wide datasets; 2) Expanded visual display of gene associations for genome-wide variants (SNPs, indels, CNVs), including Manhattan plots, 2D and 3D snapshots of any gene region, and a dynamic genome browser illustrating gene association chromosomal regions; 3) Real-time validation/replication …

Their Bugs Are Worse Than Their Bite: Emerging Infectious Disease And The Human-Animal Interface, Michael Greger

Michael Greger, MD, FACLM

In the twenty-five years since that announcement, what we now know as AIDS has killed 20 million people (National AIDS Trust 2005). Where did the AIDS virus— and other emerging diseases, such as severe acute respiratory syndrome (SARS), Ebola, mad cow— come from?

Increasing Strength And Muscle Mass In Hiv+ Men Recovering From Substance Abuse, Carianne M. Cregar, Jakob L. Vingren, John H. Curtis, Kiannah Williams, Julius F. Cantu, David W. Hill

International Journal of Exercise Science: Conference Proceedings

The combination of substance (drug and/or alcohol) abuse and infection with human immunodeficiency virus (HIV) can result in the development of several co-morbidities, including muscle wasting. Resistance training could, therefore, be an important tool in the treatment of substance addiction/abuse and HIV. PURPOSE: The purpose of this study was to examine the effect of resistance training on measures of muscle mass and strength in the context of co-occurring substance abuse and HIV. METHODS: Seventeen untrained men (Mean ± SD: 42 ± 11 years, 89.7 ± 16.0 kg, 179.7 ± 9.1 cm, 18.9 ± 5.5 %fat) who are infected with …

Study Guide For United In Anger: A History Of Act Up, Matt Brim

Open Educational Resources

The United in Anger Study Guide facilitates classroom and activist engagement with Jim Hubbard’s 2012 documentary, United in Anger: A History of ACT UP. The Study Guide contains discussion sections, projects and exercises, and resources for further research about the activism of the New York chapter of ACT UP (AIDS Coalition to Unleash Power). The Study Guide is a free, interactive, multimedia resource for understanding the legacy of ACT UP, the film’s role in preserving that legacy, and its meaning for viewers' lives.

Risky Behaviour And Hiv Prevalence Among Zambian Men, Nisha Malhotra, Jonathan Young

Nisha Malhotra

The objective of this paper is to identify demographic, social and behavioural risk factors for HIV infection among men in Zambia. In particular, the role of alcohol, condom use, and number of sex partners is highlighted as being significant in the prevalence of HIV. Multivariate Logistic Regressions were used to analyse the latest cross-sectional population-based demographic health survey for Zambia (2007). The survey included socio-economic variables and HIV serostatus for consenting men (N = 4,434). Risk for HIV was positively related to the wealth status. Men who considered themselves to be at high risk for HIV-positive were most likely to …

Time Will Tell: Community Acceptability Of Hiv Vaccine Research Before And After The "Step Study" Vaccine Discontinuation, Paula M. Frew, Mark J. Mulligan, Su-I Hou, Kayshin Chan, Carlos Del Rio

Environmental & Occupational Health Faculty Publications

Objective This study examines whether men-who-have-sex-with-men (MSM) and transgender (TG) persons’ attitudes, beliefs, and risk perceptions toward human immunodeficiency virus (HIV) vaccine research have been altered as a result of the negative findings from a phase 2B HIV vaccine study. Design We conducted a cross-sectional survey among MSM and TG persons (N = 176) recruited from community settings in Atlanta from 2007 to 2008. The first group was recruited during an active phase 2B HIV vaccine trial in which a candidate vaccine was being evaluated (the “Step Study”), and the second group was recruited after product futility was widely reported …

An Assessment Of The Role Of Chimpanzees In Aids Vaccine Research, Jarrod Bailey

Laboratory Experiments Collection

Prior to Simian Immunodeficiency Virus (SIV)-infected macaques becoming the ‘model of choice’ in the 1990s, chimpanzees were widely used in AIDS vaccine research and testing. Faced with the continued failure to develop an effective human vaccine, some scientists are calling for a return to their widespread use. To assess the past and potential future contribution of chimpanzees to AIDS vaccine development, databases and published literature were systematically searched to compare the results of AIDS vaccine trials in chimpanzees with those of human clinical trials, and to determine whether the chimpanzee trials were predictive of the human response. Protective and/or therapeutic …

Franklin Pierce Law Center Educational Report: Patent Landscape Of Dna Vaccines For Hiv, Jon R. Cavicchi, Stanley P. Kowalski

Law Faculty Scholarship

No abstract provided.

Their Bugs Are Worse Than Their Bite: Emerging Infectious Disease And The Human-Animal Interface, Michael Greger

State of the Animals 2007

In the twenty-five years since that announcement, what we now know as AIDS has killed 20 million people (National AIDS Trust 2005). Where did the AIDS virus— and other emerging diseases, such as severe acute respiratory syndrome (SARS), Ebola, mad cow— come from?

Bioorganic Studies In Aids: Synthetic Antifungals Against Pneumocystis Carinii Based On The Multivalency Concept, Langu Peng, Cunxiang Chen, Christian R. Gonzalez, Valeria Balogh-Nair

Publications and Research

We report the syntheses of antifungals containing the novel pharmacophores: oxaziridines, sulfonyloxaziridines, nitrones and nitronyl nitroxides. We hypothesized that multiple copies of the pharmacophore per molecule might be a prerequisite to enhance efficacy against the opportunistic pathogen, Pneumocystis carinii. Therefore structural optimization of the leads was based on this new “multivalency” approach. All bisoxaziridines were inactive, but a trisoxaziridine caused ca. 50% reduction of the number of P. carinii tropozoites, compared to TMP-SMX, and a hexaoxaziridine at 1 µg/ml showed activity comparable to the currently used drug, TMP-SMX. Insertion of three units of the nitronyl nitroxide pharmacophore per molecule afforded …

Efficacy And Safety Of Fluconazole Combined With Amphotericin B For Treatment Of Cryptococcal Meningitis In Patients With Aids(ประสิทธิผลและความปลอดภัยของการใช้ฟลูโคนาโซ..., Chankig Puttilerpong, Somsit Tansuphaswadikul, Duangchit Panomvana Na Ayudhya

The Thai Journal of Pharmaceutical Sciences

Cryptococcal meningitis (CM) is the most common life-threatening opportunistic fungal infection in patients with AIDS. The purpose of this study was to compare the efficacy and safety of giving high dose of amphotericin B for the first two weeks of thera...

Phenotypic Expressions Of Ccr5-Δ32/Δ32 Homozygosity, Giang T. Nguyen, Mary Carrington, Judith A. Beeler, Michael Dean, Louis M. Aledort, Philip M. Blatt, Alan R. Cohen, Donna Dimichele, M. Elaine Eyster, Craig M. Kessler, Barbara Konkle, Cindy Leissinger, Naomi Luban, Stephen J. O'Brien, James J. Goedert, Thomas R. O'Brien

Biology Faculty Articles

Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Δ32/Δ32 homozygous genotype has phenotypic expressions other than those related to HIV-1.

Design: Study subjects were white homosexual men or men with hemophilia who were not infected with HIV-1. In this study, 15 CCR5-Δ32/Δ32 homozygotes were compared with 201 CCR5 wild-type (+/+) subjects for a wide range of clinical conditions and laboratory assay results ascertained during prospective cohort studies and routine clinical care. CCR5-Δ32 genotype was determined by polymerase chain reaction, followed by single-stranded conformational polymorphism analysis.

Results: …