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Does Etravirine Decrease Central Nervous System (Cns)/Neuropsychiatric (Nps) Adverse Events Compared To Efavirenz, In Hiv Positive Patients?, Angelo D. T. Smith

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Etravirine (ETR) decreases adverse reactions on the central nervous system (CNS) compared to Efavirenz (EFV) in Human Immunodeficiency Virus (HIV) positive patients.

STUDY DESIGN: Review of three, English language, primary randomized controlled trial studies published in 2011.

DATA SOURCES: Three randomized controlled trials studying the possible decrease of ADR’s in HIV positive patients who are taking Efavirenz compared to study medication Etravirine.

OUTCOME(S) MEASURED: Outcomes measured were by surveys from patients that assess the development or cessation of CNS ADR’s. The self …

Historical Remedies Versus Current Pathogens : Laboratory Investigation Of The Efficacy Of Traditional Herbal Remedies Against Present-Day Common Causes Of Bacterial Pneumonia, Eibhlin Mccarthy

Theses

Despite the medical advances of recent years, pneumonia is still a common disease in Ireland, accounting for approximately 7% of deaths in this country'. While national databases such as those run by CIDR and SARI ensure that incidences of systemic and notifiable infections such as tuberculosis are recorded, there are currently no available statistics on commonplace respiratory isolates within Ireland. This study analysed the available data on bacterial pathogens isolated from respiratory samples at a 355 bed Irish hospital over a one year period. Seasonal variations and resistance patterns were noted. The most frequently isolated pathogens were Staphylococcus aureus (27%), …

Investigating The Role For Il-21 In Rabies Virus Vaccine-Induced Immunity., Corin L Dorfmeier, Evgeni P Tzvetkov, Anthony Gatt, James P Mcgettigan

Department of Microbiology and Immunology Faculty Papers

Over two-thirds of the world's population lives in regions where rabies is endemic, resulting in over 15 million people receiving multi-dose post-exposure prophylaxis (PEP) and over 55,000 deaths per year globally. A major goal in rabies virus (RABV) research is to develop a single-dose PEP that would simplify vaccination protocols, reduce costs associated with RABV prevention, and save lives. Protection against RABV infections requires virus neutralizing antibodies; however, factors influencing the development of protective RABV-specific B cell responses remain to be elucidated. Here we used a mouse model of IL-21 receptor-deficiency (IL-21R-/-) to characterize the role for IL-21 in RABV …

Comparison Of Heterologous Prime-Boost Strategies Against Human Immunodeficiency Virus Type 1 Gag Using Negative Stranded Rna Viruses., Tessa M Lawrence, Celestine N Wanjalla, Emily A Gomme, Christoph Wirblich, Anthony Gatt, Elena Carnero, Adolfo García-Sastre, Douglas S Lyles, James P Mcgettigan, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

This study analyzed a heterologous prime-boost vaccine approach against HIV-1 using three different antigenically unrelated negative-stranded viruses (NSV) expressing HIV-1 Gag as vaccine vectors: rabies virus (RABV), vesicular stomatitis virus (VSV) and Newcastle disease virus (NDV). We hypothesized that this approach would result in more robust cellular immune responses than those achieved with the use of any of the vaccines alone in a homologous prime-boost regimen. To this end, we primed BALB/c mice with each of the NSV-based vectors. Primed mice were rested for thirty-five days after which we administered a second immunization with the same or heterologous NSV-Gag viruses. …

Isolated Laryngeal Leishmaniasis In Immunocompetent Patients: An Underdiagnosed Disease., Salvatore Cocuzza, Alessio Strazzulla, Marilia Rita Pinzone, Stefano Cosentino, Agostino Serra, Rosario Caltabiano, Salvatore Lanzafame, Bruno Cacopardo, Giuseppe Nunnari

Department of Microbiology and Immunology Faculty Papers

We describe a case of isolated primary laryngeal leishmaniasis in an immunocompetent Italian patient with a previous medical history negative for visceral or cutaneous leishmaniasis, presenting with hoarseness. We also summarize the epidemiological, clinical, and diagnostic features and the therapeutic management of other cases of laryngeal leishmaniasis in immunocompetent subjects, described in the literature. Considering the insidious and nonspecific clinical presentation, the increasing number of different forms of mild or underestimated immunosuppressive conditions, and the number of people travelling in endemic zones, along with the ability of Leishmania amastigotes to survive for a long period in the body, we believe …

Two Coiled-Coil Domains Of Chlamydia Trachomatis Inca Affect Membrane Fusion Events During Infection., Erik Ronzone, Fabienne Paumet

Department of Microbiology and Immunology Faculty Papers

Chlamydia trachomatis replicates in a parasitophorous membrane-bound compartment called an inclusion. The inclusions corrupt host vesicle trafficking networks to avoid the degradative endolysosomal pathway but promote fusion with each other in order to sustain higher bacterial loads in a process known as homotypic fusion. The Chlamydia protein IncA (Inclusion protein A) appears to play central roles in both these processes as it participates to homotypic fusion and inhibits endocytic SNARE-mediated membrane fusion. How IncA selectively inhibits or activates membrane fusion remains poorly understood. In this study, we analyzed the spatial and molecular determinants of IncA's fusogenic and inhibitory functions. Using …

Towards Defining The Chloroviruses: A Genomic Journey Through A Genus Of Large Dna Viruses, Adrien Jeanniard, David D. Dunigan, James Gurnon, Irina V. Agarkova, Ming Kang, Jason Vitek, Garry Duncan, O William Mcclung, Megan Larsen, Jean-Michel Claverie, James L. Van Etten, Guillaume Blanc

Nebraska Center for Virology: Faculty Publications

Background: Giant viruses in the genus Chlorovirus (family Phycodnaviridae) infect eukaryotic green microalgae. The prototype member of the genus, Paramecium bursaria chlorella virus 1, was sequenced more than 15 years ago, and to date there are only 6 fully sequenced chloroviruses in public databases. Presented here are the draft genome sequences of 35 additional chloroviruses (287 – 348 Kb/319 – 381 predicted protein encoding genes) collected across the globe; they infect one of three different green algal species. These new data allowed us to analyze the genomic landscape of 41 chloroviruses, which revealed some remarkable features about these viruses. …

Evaluation Of Higher Plant Virus Resistance Genes In The Green Alga, Chlorella Variabilis Nc64a, During The Early Phase Of Infection With Paramecium Bursaria Chlorella Virus-1, Janet M. Rowe, David D. Dunigan, Guillaume Blanc, James R. Gurnon, Yuannan Xia, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

With growing industrial interest in algae plus their critical roles in aquatic systems, the need to understand the effects of algal pathogens is increasing. We examined a model algal host–virus system, Chlorella variabilis NC64A and virus, PBCV-1. C. variabilis encodes 375 homologs to genes involved in RNA silencing and in response to virus infection in higher plants. Illumina RNA-Seq data showed that 325 of these homologs were expressed in healthy and early PBCV-1 infected (≤60 min) cells. For each of the RNA silencing genes to which homologs were found, mRNA transcripts were detected in healthy and infected cells. C. variabilis …

A Twin-Cysteine Motif In The V2 Region Of Gp120 Is Associated With Siv Envelope Trimer Stabilization, Christopher Bohl, Dane Bowder, Jesse Thompson, Levon Abrahamyan, Sandra Gonzalez-Ramirez, Youdong Mao, Joseph Sodroski, Charles Wood, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The V1 and V2 variable regions of the primate immunodeficiency viruses contribute to the trimer association domain of the gp120 exterior envelope glycoprotein. A pair of V2 cysteine residues at 183 and 191 (‘‘twin cysteines’’) is present in several simian immunodeficiency viruses, human immunodeficiency virus type 2 (HIV-2) and some SIV_cpz lineages, but not in HIV-1. To examine the role of this potentially disulfide-bonded twin-cysteine motif, the cysteine residues in the SIVmac239 envelope glycoproteins were individually and pairwise substituted by alanine residues. All of the twin-cysteine mutants exhibited decreases in gp120 association with the Env trimer, membrane-fusing activity, and …

Hiv-1 Env C2-V4 Diversification In A Slow-Progressor Infant Reveals A Flat But Rugged Fitness Landscape, S. Abigail Smith, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type-1 (HIV-1) fitness has been associated with virus entry, a process mediated by the envelope glycoprotein (Env). We previously described Env genetic diversification in a Zambian, subtype C infected, slow-progressor child (1157i) in parallel with an evolving neutralizing antibody response. Because of the role the Variable-3 loop (V3) plays in transmission, cell tropism, neutralization sensitivity, and fitness, longitudinally isolated 1157i C2-V4 alleles were cloned into HIV-1_NL4-3-eGFP and -DsRed2 infectious molecular clones. The fluorescent reporters allowed for dual-infection competitions between all patient-derived C2-V4 chimeras to quantify the effect of V3 diversification and selection on fitness. ‘Winners’ …

‘‘Megavirales’’, A Proposed New Order For Eukaryotic Nucleocytoplasmic Large Dna Viruses, Philippe Colson, Xavier De Lamballerie, Natalya Yutin, Sassan Asgari, Yves Bigot, Dennis K. Bideshi, Xiao-Wen Cheng, Brian A. Federici, James L. Van Etten, Eugene V. Koonin, Bernard La Scola, Didier Raoult

Nebraska Center for Virology: Faculty Publications

The nucleocytoplasmic large DNA viruses (NCLDVs) comprise a monophyletic group of viruses that infect animals and diverse unicellular eukaryotes. The NCLDV group includes the families Poxviridae, Asfarviridae, Iridoviridae, Ascoviridae, Phycodnaviridae, Mimiviridae and the proposed family ‘‘Marseilleviridae’’. The family Mimiviridae includes the largest known viruses, with genomes in excess of one megabase, whereas the genome size in the other NCLDV families varies from 100 to 400 kilobase pairs. Most of the NCLDVs replicate in the cytoplasm of infected cells, within so-called virus factories. The NCLDVs share a common ancient origin, as demonstrated by evolutionary reconstructions that trace approximately 50 genes encoding …

Recent Advances On The Use Of Structural Biology For The Design Of Novel Envelope Immunogens Of Hiv-1, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Many efforts have been made in the worldwide quest for a prophylactic HIV vaccine to end the AIDS pandemic, but none has yet succeeded. The lessons learned have repeatedly informed us that the traditional or conventional approaches directly using the pathogens or subunits will not be sufficient for an effective HIV/AIDS vaccine. Recent advances in structure-based technology have shown some promise in the quest for a better immunogen in HIV vaccine development. According to the basic binding structural relationship of an antigen and an antibody, structure-based antigen design could bring some hope for the development of an effective vaccine against …

The Highly Conserved Layer-3 Component Of The Hiv-1 Gp120 Inner Domain Is Critical For Cd4-Required Conformational Transitions, Anik Désormeaux, Mathieu Coutu, Halima Medjahed, Beatriz Pacheco, Alon Herschhorn, Christopher Gu, Shi-Hua Xiang, Youdong Mao, Joseph Sodroski, Andrés Finzi

Nebraska Center for Virology: Faculty Publications

The trimeric envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) mediates virus entry into host cells. CD4 engagement with the gp120 exterior envelope glycoprotein subunit represents the first step during HIV-1 entry. CD4-induced conformational changes in the gp120 inner domain involve three potentially flexible topological layers (layers 1, 2, and 3). Structural rearrangements between layer 1 and layer 2 have been shown to facilitate the transition of the envelope glycoprotein trimer from the unliganded to the CD4-bound state and to stabilize gp120-CD4 interaction. However, our understanding of CD4-induced conformational changes in the gp120 inner domain remains incomplete. Here, …

Analysis Of Primary Resistance Mutations To Hiv-1 Entry Inhibitors In Therapy Naive Subtype C Hiv-1 Infected Mother– Infant Pairs From Zambia, Hongyan Guo, Chang Liu, Bin Liu, Charles Wood, Xiaohong Kong

Nebraska Center for Virology: Faculty Publications

Background—Small molecular CCR5 inhibitors represent a new class of drugs for treating HIV-1 infection. The evaluation of the primary resistance mutations associated with entry inhibitors during HIV-1 perinatal transmission is required because they may have a profound impact on the clinical management in MTCT.

Objectives—To evaluate the primary resistance mutations to maraviroc and vicriviroc during perinatal transmission and analyze the sensitivity of Env derived from mother–infant pairs to maraviroc.

Study design—Nine MIPs infected by subtype C HIV-1 were recruited to analyze the prevalence and transmission of primary resistance mutations to maraviroc and vicriviroc. Moreover, Env derived from six MIPs were …

Early Childhood Infection Of Kaposi’S Sarcoma-Associated Herpesvirus In Zambian Households: A Molecular Analysis, Landon Olp, Danielle M. Shea, Maxine K. White, Clement Gondwe, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Sub-Saharan Africa is endemic for Kaposi’s sarcoma-associated herpesvirus (KSHV) and there is a high rate of early childhood infection; however, the transmission sources are not well characterized. We examined household members as potential KSHV transmission sources to young children in the KSHV-endemic country of Zambia. To this end, we enrolled and followed Zambian households with at least one KSHV-seropositive child and collected longitudinal buccal swab samples. KSHV burden was evaluated and K1 sequences from the children were determined and analyzed for differences to K1 sequences from household members. The K1 sequences were also analyzed for evolution over time. We generated …

A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness Of Staphylococcus Epidermidis During Β-Lactam Stress, Vinai Chittenzham Thomas, Lauren Kinkhead, Ashley Janssen, Carolyn Schaeffer, Keith Woods, Jill Lindgren, Johnathan Peaster, Sujata Chaudhari, Marat Sadykov, Joselyn Jones, Sameh Mohamadi Abdelghani, Matthew Zimmerman, Kenneth W. Bayles, Greg Somerville, Paul Fey

School of Veterinary and Biomedical Sciences: Faculty Publications

A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these …

Manipulation Of Cellular Processing Bodies And Their Constituents By Viruses, Asit K. Pattnaik, Phat X. Dinh

School of Veterinary and Biomedical Sciences: Faculty Publications

The processing bodies (PBs) are a form of cytoplasmic aggregates that house the cellular RNA decay machinery as well as many RNA-binding proteins and mRNAs. The PBs are constitutively present in eukaryotic cells and are involved in maintaining cellular homeostasis by regulating RNA metabolism, cell signaling, and survival. Virus infections result in modification of the PBs and their constituents. Many viruses induce compositionally altered PBs, while many others use specific components of the PBs for their replication. PB constituents are also known to restrict virus replication by a variety of mechanisms. Further, continuing studies in this rapidly emerging field of …

Characterization Of A Serologic Marker Candidate For Development Of A Live-Attenuated Diva Vaccine Against Porcine Reproductive And Respiratory Syndrome Virus, Hiep Vu, Byungjoon Kwon, Marcelo De Lima, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

DIVA (differentiating infected from vaccinated animals) vaccines have proven extremely useful for control and eradication of infectious diseases in livestock. We describe here the characterization of a serologic marker epitope, so-called epitope-M201, which can be a potential target for development of a live-attenuated DIVA vaccine against porcine reproductive and respiratory syndrome virus (PRRSV). Epitope-M201 is located at the carboxyl terminus (residues 161-174) of the viral M protein. The epitope is highly immunodominant and well-conserved among type-II PRRSV isolates. Rabbit polyclonal antibodies prepared against this epitope are non-neutralizing; thus, the epitope does not seem to contribute to the protective immunity against …

Trex1 Regulates Lysosomal Biogenesis And Interferon-Independent Activation Of Antiviral Genes, Maroof Hasan, James Koch, Dinesh Rakheja, Asit K. Pattnaik, James Brugarolas, Igor Dozmorov, Beth Levine, Edward K. Wakeland, Min Ae Lee-Kirsch, Nan Yan

School of Veterinary and Biomedical Sciences: Faculty Publications

Innate immune sensing of viral nucleic acids triggers type I interferon (IFN) production, which activates interferon-stimulated genes (ISGs) and directs a multifaceted antiviral response. ISGs can also be activated through IFN-independent pathways, although the precise mechanisms remain elusive. Here we found that the cytosolic exonuclease Trex1 regulates the activation of a subset of ISGs independently of IFN. Both Trex1−/− mouse and TREX1-mutant human cells express high levels of antiviral genes and are refractory to viral infections. The IFN-independent activation of antiviral genes in Trex1−/− cells requires STING, TBK1 and IRF3 and IRF7. We also found that Trex1-deficient cells display expanded …

Influence Of Therapeutic Ceftiofur Treatments Of Feedlot Cattle On Fecal And Hide Prevalences Of Commensal Escherichia Coli Resistant To Expanded-Spectrum Cephalosporins, And Molecular Characterization Of Resistant Isolates, John W. Schmidt, Dee Griffin, Larry A. Kuehn, Dayna M. Brichta-Harhay

School of Veterinary and Biomedical Sciences: Faculty Publications

In the United States, the bla_CMY-2 gene contained within incompatibility type A/C (IncA/C) plasmids is frequently identified in extended-spectrum-cephalosporin-resistant (ESC^r) Escherichia coli strains from both human and cattle sources. Concerns have been raised that therapeutic use of ceftiofur in cattle may increase the prevalence of ESC^r E. coli. We report that herd ESC^r E. coli fecal and hide prevalences throughout the residency of cattle at a feedlot, including during the period of greatest ceftiofur use at the feedlot, were either not significantly different (P≥0.05) or significantly less (Pr E. coli shedding that follows ceftiofur …

Complete Closed Genome Sequences Of Mannheimia Haemolytica Serotypes A1 And A6, Isolated From Cattle, Gregory P. Harhay, Sergey Koren, Adam M. Phillippy, D. Scott Mcvey, Jennifer Kuszak, Michael L. Clawson, Dayna M. Harhay, Michael P. Heaton, Carol G. Chitko-Mckown, Timothy P. L. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Mannheimia haemolytica is a respiratory pathogen affecting cattle and related ruminants worldwide. M. haemolytica is commonly associated with bovine respiratory disease complex (BRDC), a polymicrobial multifactorial disease.Wepresent the first two complete closed genome sequences of this species, determined using an automated assembly pipeline requiring no manual finishing.

Deep Sequencing And Genome-Wide Analysis Reveals The Expansion Of Microrna Genes In The Gall Midge Mayetiola Destructor, Chitvan Khajuria, Christie E. Williams, Mustapha El Bouhssini, R. Jeff Whitworth, Stephen Richards, Jeffrey J. Stuart, Ming-Shun Chen

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating post transcriptional gene expression. Gall midges encompass a large group of insects that are of economic importance and also possess fascinating biological traits. The gall midge Mayetiola destructor, commonly known as the Hessian fly, is a destructive pest of wheat and model organism for studying gall midge biology and insect – host plant interactions.

Results: In this study, we systematically analyzed miRNAs from the Hessian fly. Deep-sequencing a Hessian fly larval transcriptome led to the identification of 89 miRNA species that are either identical or very …

Development And Evaluation Of A Replicon Particle Vaccine Expressing The E2 Glycoprotein Of Bovine Viral Diarrhea Virus (Bvdv) In Cattle, John Dustin Loy, Jill Gander, Mark Mogler, Ryan Vander Veen, Julia Ridpath, Delbert Hank Harris, Kurt Kamrud

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Bovine viral diarrhea virus is one of the most significant and costly viral pathogens of cattle worldwide. Alphavirus-derived replicon particles have been shown to be safe and highly effective vaccine vectors against a variety of human and veterinary pathogens. Replicon particles are non-propagating, DIVA compatible, and can induce both humoral and cell mediated immune responses. This is the first experiment to demonstrate that Alphavirus-based replicon particles can be utilized in a standard prime/boost vaccination strategy in calves against a commercially significant bovine pathogen.

Findings: Replicon particles that express bovine viral diarrhea virus sub-genotype 1b E2 glycoprotein were …

Selection And Evolution Of Pneumococci In Response To Conjugate Vaccines, Christina M. Croney

All ETDs from UAB

Pneumococcal conjugate vaccines (PCVs) containing subsets of the >90 capsular polysaccharide antigens have been successful as a means of decreasing invasive and non-invasive pneumococcal disease worldwide. However, this success is limited to the specif-ic capsular serotypes against which PCVs are formulated and studies have reported the increase of nonvaccine serotypes. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the United States in 2010 for the prevention of invasive pneumococcal disease (IPD) and otitis media and was released without efficacy data. In this study we set out to 1) determine potential efficacy for invasive and noninvasive pneumococcal disease and 2) …

Neutropenia And Progenitor Cell Mobilization In Ap3-B1 Mutant Pearl Mice, Matthew Vallejo

All ETDs from UAB

Mutations in the AP3-ß1 gene are known to cause Hermansky-Pudlak syndrome type 2 (HPS2) in humans and canine cyclic hematopoiesis (CH) in gray collie dogs. HPS2 patients have severe congenital neutropenia (SCN), and dogs have cyclic neutropenia (CN). The mechanism behind neutropenia is uncertain. Pearl mice have an AP3-ß1 mutation, but whether they actually have neutropenia has not yet been evaluated. This dissertation presents a discussion of the evaluation of neutropenia in pearl mice, hematopoietic progenitor cell mobilization defect in pearl mice and finally an evaluation of methods of dog-to-mouse xenotransplantation to establish a xenotransplant model of the dog hematopoietic …

Potential Roles Of The Immunostimulatory Signals Il-15 And Mica In Oncolytic Hsv-1 Therapy For Malignant Glioma, David Curtis Gaston

All ETDs from UAB

Malignant gliomas are the most frequently diagnosed and the most fatal primary brain tumors. Innovative therapeutic approaches are necessary to combat these devastating cancers, and oncolytic herpes simplex virus type-1 (oHSV) deleted of the γ134.5 neurovirulence gene is a promising adjunctive therapy. The primary mechanism of tumor clearance by oHSV is lytic replication specifically within malignant cells. oHSV also stimulates tumor infiltration of cytotoxic immune effector cells that can participate in tumor clearance. However, cytotoxic immune cells target oHSV as well as tumor, which may limit therapeutic efficacy. Further knowledge regarding the nature of these interactions and how the interactions …

Adapter Based Strategies For Adenovirus Vector Retargeting To T Lymphocytes, Matthew S. Beatty

All ETDs from UAB

Adenoviruses are the most commonly used gene therapy vector for cancer therapy clinical trials. While adenovirus has shown a great track record in a variety of cancer therapeutics it has not progressed as a vector system for the modification of T lymphocytes. One of the major roadblocks towards utilizing adenovirus for T cell therapy is the lack of coxsackie virus and adenovirus receptor on the cell surface of T cell lineages. Exploitation of alternative receptors has allowed adenovirus vectors to be utilized in a variety of cell types that native adenovirus type 5 cannot infect. Thus, retargeting adenovirus to an …

Intracellular Quantitation And Pharmacokinetic Modeling Of Nucleoside Analogs In The Female Genital Tract, Amanda Marie James

All ETDs from UAB

Human Immunodeficiency Virus (HIV) is one of the leading infectious diseases in the world. In spite of substantial progress in the advancement of antiretroviral therapy for HIV treatment, new infections outpace the number of infected persons initiating ART. Therefore, the prevention of HIV remains a crucial health issue. Pre-Exposure Prophylaxis, (PrEP), which involves using one or more antiretroviral agents to reduce the risk of HIV infection prior to potential exposure, has shown effectiveness at reducing HIV transmission in study volunteers with different sexual orientation around the world. The clinical pharmacology of antiretroviral drugs, specifically tenofovir (TFV) and emtricitabine (FTC), in …

The Role Of Complement In Experimental Cerebral Malaria, Theresa N. Ramos

All ETDs from UAB

Cerebral malaria (CM) is one of the most severe clinical complications of P. falciparum malaria with a fatality rate of 15-30%, and 10% of CM survivors have permanent neurological sequelae. Since inflammation is a central pathophysiological tenet of CM, we began examining the role of the complement system in pathogenesis of experimental cerebral malaria (ECM) using Plasmodium berghei ANKA (PbA) model. Previous studies using this model indicated that mice naturally deficient in complement component C5 were protected from cerebral complications, and wild type mice treated with anti-C5aR antibody were also protected. To determine the protective mechanism of naturally-C5 deficient mice, …

Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah

All ETDs from UAB

Fc receptors provide an interface between humoral immunity and cellular immunity by binding to the Fc portion of immunoglobulin and mediating effector functions. Cells expressing Fc receptors play a major role in immune complex clearance via phagocytosis, leading to a context dependent pro- or anti-inflammatory environment. Signaling by multi-chain Fc receptor complexes, including FcgRI, FcgRIII, FceRI and FcaRI is mediated by the ITAM-containing common FceRIg (g-chain) subunit. However, despite the use of a common g-chain, different Fc receptor complexes elicit specific cellular programs, suggesting additional layers of regulation of tyrosine based signaling by g-chain. We hypothesized that the unique g-chain …