Medical Specialties Commons^™

Low-Abundance Resistant Mutations In Hiv-1 Subtype C Antiretroviral Therapy-Naïve Individuals As Revealed By Pyrosequencing, Sandra Gonzalez, Damien C. Tully, Clement Gondwe, Charles Wood

Nebraska Center for Virology: Faculty Publications

Given the recent scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, we sought to determine how often and at what levels do drug-resistant mutant variants exist in ART-naïve HIV subtype C infected individuals. Samples from 10 ART-naïve Zambian individuals were subjected to ultra-deep pyrosequencing (UDPS) to characterize the frequency of low-abundance drug resistance mutations in the pol gene. Low-abundance clinically relevant variants were detected for nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in eight of the ten subjects. Intermediate to high-level resistance was predicted for the majority of NRTIs. Mutations conferring resistance to …

Clade C Hiv-1 Isolates Circulating In Southern Africa Exhibit A Greater Frequency Of Dicysteine Motif-Containing Tat Variants Than Those In Southeast Asia And Cause Increased Neurovirulence, Vasudev R. Rao, Ujjwal Neogi, Joshua S, Talboom, Ligia Padilla, Mustafizur Rahman, Cari Fritz-French, Sandra Gonzalez-Ramirez, Anjali Verma, Charles Wood, Ruth M. Ruprecht, Udaykumar Ranga, Tasnim Azim, Vinayaka R. Prasad

Nebraska Center for Virology: Faculty Publications

Background: HIV-1 Clade C (Subtype C; HIV-1C) is responsible for greater than 50% of infections worldwide. Unlike clade B HIV-1 (Subtype B; HIV-1B), which is known to cause HIV associated dementia (HAD) in approximately 15% to 30% of the infected individuals, HIV-1C has been linked with lower prevalence of HAD (0 to 6%) in India and Ethiopia. However, recent studies report a higher prevalence of HAD in South Africa, Zambia and Botswana, where HIV-1C infections predominate. Therefore, we examined whether Southern African HIV-1C is genetically distinct and investigated its neurovirulence. HIV-1 Tat protein is a viral determinant of neurocognitive dysfunction. …

Global Neuroaids Roundtable, Jeymohan Joseph, Cristian L. Achim, Michael J. Boivin, Bruce J. Brew, David B. Clifford, Deborah A. Colosi, Ronald J. Ellis, Robert K. Heaton, Amadou Gallo-Diop, Igor Grant, Georgette D. Kanmogne, Mahendra Kumar, Scott Letendre, Thomas D. Marcotte, Avindra Nath, Carlos A. Pardo, Robert H. Paul, Lynn Pulliam, Kevin Robertson, Walter Royal Iii, Ned Sacktor, Pasiri Sithinamsuwan, Davey M. Smith, Victor Valcour, Brian Wigdahl, Charles Wood

Nebraska Center for Virology: Faculty Publications

In May 2012, the Division of AIDS Research at the National Institute of Mental Health (NIMH) organized the “Global NeuroAIDS Roundtable” in conjunction with the 11th International Symposium on Neurovirology and the 2012 Conference on HIV in the Nervous System. The meeting was held in New York, NY, USA and brought together NIMH-funded investigators who are currently working on projects related to the neurological complications of AIDS (NeuroAIDS) in Africa, Asia, Eastern Europe, and Latin America in order to provide an opportunity to share their recent findings and discuss the challenges encountered within each country. The major goals of the …

Relevance Of Molecular Mimicry In The Mediation Of Infectious Myocarditis, Chandirasegaran Massilamany, Sally A. Huber, Madeleine W. Cunningham, Jay Reddy

Jay Reddy Publications

Heart disease, the leading cause of death in humans, is estimated to affect one in four American adults in some form. One predominant cause of heart failure in young adults is myocarditis, which can lead to the development of dilated cardiomyopathy, a major indication for heart transplantation. Environmental microbes, including viruses, bacteria, and fungi that are otherwise innocuous, have the potential to induce inflammatory heart disease. As the list is growing, it is critical to determine the mechanisms by which microbes can trigger heart autoimmunity and, importantly, to identify their target antigens. This is especially true as microbes showing structural …

Digestibility And Ige-Binding Of Glycosylated Codfish Parvalbumin, Harmen H. J. De Jongh, Carlos López Robles, Eefjan Timmerman, Julie A. Nordlee, Poi-Wah Lee, Joseph L. Baumert, Robert G. Hamilton, Steve L. Taylor, Stef J. Koppelman

Department of Food Science and Technology: Faculty Publications

Food-processing conditions may alter the allergenicity of food proteins by different means. In this study, the effect of the glycosylation as a result of thermal treatment on the digestibility and IgE-binding of codfish parvalbumin is investigated. Native and glycosylated parvalbumins were digested with pepsin at various conditions relevant for the gastrointestinal tract. Intact proteins and peptides were analysed for apparent molecular weight and IgE-binding. Glycosylation did not substantially affect the digestion. Although the peptides resulting from digestion were relatively large (3 and 4 kDa), the IgE-binding was strongly diminished. However, the glycosylated parvalbumin had a strong propensity to form dimers …

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 …

Delayed Amyloid Plaque Deposition And Behavioral Deficits In Outcrossed Aβpp/Ps1 Mice, Brian A. Couch, Meghan E. Kerrisk, Adam C. Kaufman, Haakon B. Nygaard, Stephen M. Strittmatter, Anthony J. Koleske

School of Biological Sciences: Faculty Publications

Alzheimer’s disease (AD) is a progressive neurodegenerative dementia characterized by amyloid plaque accumulation, synapse/dendrite loss, and cognitive impairment. Transgenic mice expressing mutant forms of amyloid-β precursor protein (AβPP) and presenilin-1 (PS1) recapitulate several aspects of this disease and provide a useful model system for studying elements of AD progression. AβPP/PS1 mice have been previously shown to exhibit behavioral deficits and amyloid plaque deposition between 4–9 months of age. We crossed AβPP/PS1 animals with mice of a mixed genetic background (C57BL/6 × 129/SvJ) and investigated the development of AD-like features in the resulting outcrossed mice. The onset of memory-based behavioral impairment …

Severe Reactions To A Soy Containing Beverage In Peanut Allergic Individuals Not Avoiding Soy, Benjamin Remington, Julie A. Nordlee, John R. Bacon, Marc E. Dyer, Steve L. Taylor, Joe L. Baumert

Department of Food Science and Technology: Faculty Publications

Rationale: Three peanut-allergic individuals experienced severe reactions to a nationally distributed high-protein beverage in the same month. The major protein sources in the beverage were soy-based ingredients and cows’ milk. These individuals did not avoid soy in their diet and previously consumed various soy products without adverse reactions. Peanut contamination of the beverage was not detected by specific ELISA, so attention shifted to the soy ingredients. The research objective was to elucidate differences between the soy milk and soy protein isolate used in the beverage and other forms of soy safely consumed by these individuals.

Methods: Specific IgE levels from …

Aging And Religious Participation In Late Life, Kuan-Yuan Wang

College of Education and Human Sciences: Dissertations, Theses, and Student Research

Objective: The aim of the study is to evaluate the relationship between two dimensions of religiosity, religious service attendance and religious beliefs, and the process of aging, controlling for the effects of covariates known to affect religious development among older adults.

Methods: Secondary analysis of longitudinal data from the Florida Retirement Study was used to assess the trajectories of religious development over time as modeled with two growth processes: religious service attendance and religious beliefs. We analyzed data from six interview waves (Waves 1 and 5 - 9) with 1000 older adults age 72 or over. Covariates included demographic factors …

On The Importance Of Modeling Stent Procedure For Predicting Arterial Mechanics, Shijia Zhao, Linxia Gu, Stacey R. Froemming

Department of Mechanical and Materials Engineering: Faculty Publications

The stent-artery interactions have been increasingly studied using the finite element method for better understanding of the biomechanical environment changes on the artery and its implications. However, the deployment of balloon-expandable stents was generally simplified without considering the balloon-stent interactions, the initial crimping process of the stent, its overexpansion routinely used in the clinical practice, or its recoil process. In this work, the stenting procedure was mimicked by incorporating all the above-mentioned simplifications. The impact of various simplifications on the stent-induced arterial stresses was systematically investigated. The plastic strain history of stent and its resulted geometrical variations, as well as …

Data Mining Of Pancreatic Cancer Protein Databases, Peter Revesz, Christopher Assi

School of Computing: Conference and Workshop Papers

Data mining of protein databases poses special challenges because many protein databases are non- relational whereas most data mining and machine learning algorithms assume the input data to be a type of rela- tional database that is also representable as an ARFF file. We developed a method to restructure protein databases so that they become amenable for various data mining and machine learning tools. Our restructuring method en- abled us to apply both decision tree and support vector machine classifiers to a pancreatic protein database. The SVM classifier that used both GO term and PFAM families to characterize proteins gave …

Spectrum Of Acute Clinical Characteristics Of Diagnosed Concussions In College Athletes Wearing Instrumented Helmets, Ann-Christine Duhaime,, Jonathan G. Beckwith, Arthur C. Maerlender, Thomas W. Mcallister, Joseph J. Crisco, Stefan M. Duma, P. Gunnar Brolinson, Steven Rowson, Laura A. Flashman, Jeffrey J. Chu, Richard M. Greenwald

Department of Psychology: Faculty Publications

Object. Concussive head injuries have received much attention in the medical and public arenas, as concerns have been raised about the potential shortand long-term consequences of injuries sustained in sports and other activities. While many student athletes have required evaluation after concussion, the exact definition of concussion has varied among disciplines and over time. The authors used data gathered as part of a multiinstitutional longitudinal study of the biomechanics of head impacts in helmeted collegiate athletes to characterize what signs, symptoms, and clinical histories were used to designate players as having sustained concussions.

Methods. Players on 3 college …

Measuring Parvalbumin Levels In Fish Muscle Tissue: Relevance Of Muscle Locations And Storage Conditions, Poi-Wah Lee, Julie A. Nordlee, Stef J. Koppelman, Joseph L. Baumert, Steve L. Taylor

Department of Food Science and Technology: Faculty Publications

Fish is an allergenic food capable of provoking severe anaphylactic reactions. Parvalbumin is the major allergen identified in fish and frog muscles. Antibodies against fish and frog parvalbumin have been used to quantify parvalbumin levels from fish. However, these antibodies react variably with parvalbumin from different fish species. Several factors might be responsible for this variation including instability of parvalbumin in fish muscle as a result of frozen storage and differential parvalbumin expression in muscles from various locations within the whole fish. We aimed to investigate whether these factors contribute to the previously observed variable immunoreactivity of the anti-parvalbumin antibodies. …

Parvalbumin In Fish Skin-Derived Gelatin: Is There A Risk For Fish Allergic Consumers?, S. J. Koppelman, Julie A. Nordlee, P.-W. Lee, R. P. Happe, M. Hessing, R. Norland, T. Manning, R. Deschene, G. A. H. De Jong, Steve L. Taylor

Department of Food Science and Technology: Faculty Publications

The major allergen parvalbumin was purified from cod muscle tissues, and polyclonal antibodies were raised toward it. The antibodies were tested for specificity, and an enzyme-linked immunosorbent assay (ELISA) was developed using these antibodies. The ELISA was applied to measure parvalbumin in cod skin, the starting material for fish gelatin made from deep sea, wild fish. The ELISA was sufficiently sensitive (LLOQ = 0.8 ng ml^–1 in extracts, corresponding to 0.02 μg of parvalbumin per g of tissue) and did not cross-react with common food constituents. Fish gelatin, wine, and beer, matrices for the potential use of this ELISA, …

Gut Microbiome Composition Is Linked To Whole Grain-Induced Immunological Improvements, Ines Martinez, James M. Lattimer, Kelcie L. Hubach, Jennifer A. Case, Junyi Yang, Casey G. Weber, Julie A. Louk, Devin J. Rose, Gayaneh Kyureghian, Daniel A. Peterson, Mark D. Haub, Jens Walter

Food for Health: Publications

The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on …

Composition Of The Adult Digestive Tract Bacterial Microbiome Based On Seven Mouth Surfaces, Tonsils, Throat And Stool Samples, Nicola Segata, Susan Kinder Haake, Peter Mannon, Katherine P. Lemon, Levi Waldron, Dirk Gevers, Curtis Huttenhower, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Background: To understand the relationship between our bacterial microbiome and health, it is essential to define the microbiome in the absence of disease. The digestive tract includes diverse habitats and hosts the human body’s greatest bacterial density. We describe the bacterial community composition of ten digestive tract sites from more than 200 normal adults enrolled in the Human Microbiome Project, and metagenomically determined metabolic potentials of four representative sites.

Results: The microbiota of these diverse habitats formed four groups based on similar community compositions: buccal mucosa, keratinized gingiva, hard palate; saliva, tongue, tonsils, throat; sub- and supra-gingival plaques; …

Metabolic Reconstruction For Metagenomic Data And Its Application To The Human Microbiome, Sahar Abubucker, Nicola Segata, Johannes Goll, Alyxandria M. Schubert, Jacques Izard, Brandi L. Cantarel, Beltran Rodriguez-Mueller, Jeremy Zucker, Mathangi Thiagarajan, Bernard Henrissat, Owen White, Scott T. Scott, Barbara Methé, Patrick D. Schloss, Dirk Gever, Makedonka Mitreva, Curtis Huttenhower

Department of Food Science and Technology: Faculty Publications

Microbial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such communities’ metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and metabolic potential of a microbial community metagenome. We determined the gene families and pathways present or absent within a community, as …

Improving Health Care Quality And Safety: The Development And Assessment Of Laparoscopic Surgery Instrumentation, Practices And Procedures, Bernadette Mccrory

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Adverse events due to medical errors are a leading cause of death in the United States exceeding the mortality rates of motor vehicle accidents, breast cancer and AIDS. Improvements can and should be made to reduce the rates of preventable surgical errors since they account for nearly half of all adverse events within hospitals. Although minimally invasive surgery has proven patient benefits such as reduced postoperative pain and hospital stay, its operative environment imposes substantial physical and cognitive strain on the surgeon increasing the risk of error. In order to mitigate errors and protect patients, a multidisciplinary approach was taken …

Single-Chain Vαvβ T Cell Receptors Function Without Mispairing With Endogenous Tcr Chains1, David H. Aggen, Adam S. Chervin, Thomas M. Schmitt, Boris Engels, Jennifer D. Stone, Sarah A. Richman, Kurt H. Piepenbrink, Brian M. Baker, Philip D. Greenberg, Hans Schreiber, David M. Kranz

Food for Health: Publications

Transduction of exogenous T cell receptor (TCR) genes into patients’ activated peripheral blood T cells is a potent strategy to generate large numbers of specific T cells for adoptive therapy of cancer and viral diseases. However, the remarkable clinical promise of this powerful approach is still being overshadowed by a serious potential consequence: mispairing of the exogenous TCR chains with endogenous TCR chains. These “mixed” heterodimers can generate new specificities that result in graft-versus-host reactions. Engineering TCR constant regions of the exogenous chains with a cysteine promotes proper pairing and reduces the mispairing, but, as we show here, does not …

Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus serotype (Ad5) is the most studied Ad. Ad1, 2, and 6 are also members of species C Ad and are presumed to have biologies similar to Ad5. In this work, we have compared the ability of Ad1, 2, 5, and 6 to infect liver and muscle after intravenous and intramuscular injection. We found that Ad6 was surprisingly the most potent at liver gene delivery and that Ad1 and Ad2 were markedly weaker than Ad5 and 6. To understand these differences, we sequenced the Ad6 genome. This revealed that the Ad6 fiber protein is surprisingly three shaft repeats shorter than …

Heme Oxygenase-1 Regulates The Immune Response To Influenza Virus Infection And Vaccination In Aged Mice, Nathan W. Cummins, Eric A. Weaver, Shannon M. May, Anthony J. Croatt, Oded Foreman, Richard B. Kennedy, Gregory A. Poland, Michael A. Barry, Karl A. Nath, Andrew D. Badley

Nebraska Center for Virology: Faculty Publications

Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genome-wide association study evaluated the expression of single-nucleotide polymorphisms (SNPs) in the HO-1 gene and the response to influenza vaccination in healthy humans. HO-1-deficient mice had decreased survival after influenza infection compared to WT mice (median …

Conformational Melding Permits A Conserved Binding Geometry In Tcr Recognition Of Foreign And Self Molecular Mimics, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian M. Baker

Food for Health: Publications

Molecular mimicry between foreign and self antigens is a mechanism of T cell receptor cross reactivity and is thought to contribute to the development of autoimmunity. The αβ TCR A6 recognizes the foreign antigen Tax from the virus HTLV-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease HAM/TSP, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found here that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics, and that in contrast with other recent structures …