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Articles 721 - 750 of 1178
Full-Text Articles in Medical Sciences
The Pseudorabies Virus Protein, Pul56, Enhances Virus Dissemination And Virulence But Is Dispensable For Axonal Transport, Gina R. Daniel, Patricia J. Sollars, Gary E. Pickard, Gregory A. Smith
The Pseudorabies Virus Protein, Pul56, Enhances Virus Dissemination And Virulence But Is Dispensable For Axonal Transport, Gina R. Daniel, Patricia J. Sollars, Gary E. Pickard, Gregory A. Smith
School of Veterinary and Biomedical Sciences: Faculty Publications
Neurotropic herpesviruses exit the peripheral nervous system and return to exposed body surfaces following reactivation from latency. The pUS9 protein is a critical viral effector of the anterograde axonal transport that underlies this process. We recently reported that while pUS9 increases the frequency of sorting of newly assembled pseudorabies virus particles to axons from the neural soma during egress, subsequent axonal transport of individual virus particles occurs with wild-type kinetics in the absence of the protein. Here, we examine the role of a related pseudorabies virus protein, pUL56, during neuronal infection. The findings indicate that pUL56 is a virulence factor …
Hexokinase Ii Localization Is Independent Of Ampk Activation In Hela Cells, Alyssa Brown
Hexokinase Ii Localization Is Independent Of Ampk Activation In Hela Cells, Alyssa Brown
Graduate School of Biomedical Sciences Theses and Dissertations
In order for a cancer cell to thrive, it must alter its metabolism to produce the energy needed for rapid growth. Cells accomplish this by the Warburg Effect, or switching metabolism to aerobic glycolysis, where a cell can rapidly break down sugar into ATP, lactic acid and additional byproducts. Hexokinase 2, the enzyme that catalyzes the first committed step of glycolysis, may also be upregulated in cancer cells to increase glucose breakdown. Similar proteins for metabolism are found in both S. cerevisiae and mammalian cells. S. cerevisiae regulates metabolism through glucose repression, by Snf1 (mammalian homolog: AMPK) activation, which aids …
Utility And Origin Of Blood-Based Autoantibodies For Early Detection And Diagnosis Of Neurodegenerative Diseases, Cassandra Demarshall
Utility And Origin Of Blood-Based Autoantibodies For Early Detection And Diagnosis Of Neurodegenerative Diseases, Cassandra Demarshall
Graduate School of Biomedical Sciences Theses and Dissertations
Autoantibodies are self-reactive antibodies that have been widely implicated as causal agents of autoimmune diseases. They are found in the blood of all human sera, regardless of age, gender, or the presence or absence of disease. While the underlying reason for their ubiquity remains unknown, it has been hypothesized that they participate in the clearance of blood-borne cell and tissue debris generated in both healthy and diseased individuals on a daily basis. Although much evidence supports this debris clearance role, recent studies also suggest a causal role for autoantibodies in disease. My thesis work has focused on this "cause and/or …
Mitosis In Circulating Tumor Cells Stratifies Highly Aggressive Breast Carcinomas., Daniel L. Adams, Diane K. Adams, Steingrimur Stefansson, Christian Haudenschild, Stuart S. Martin, Monica Charpentier, Saranya Chumsri, Massimo Cristofanilli, Cha-Mei Tang, R Katherine Alpaugh
Mitosis In Circulating Tumor Cells Stratifies Highly Aggressive Breast Carcinomas., Daniel L. Adams, Diane K. Adams, Steingrimur Stefansson, Christian Haudenschild, Stuart S. Martin, Monica Charpentier, Saranya Chumsri, Massimo Cristofanilli, Cha-Mei Tang, R Katherine Alpaugh
Pathology Faculty Publications
BACKGROUND: Enumeration of circulating tumor cells (CTCs) isolated from the peripheral blood of breast cancer patients holds promise as a clinically relevant, minimally invasive diagnostic test. However, CTC utility has been limited as a prognostic indicator of survival by the inability to stratify patients beyond general enumeration. In comparison, histological biopsy examinations remain the standard method for confirming malignancy and grading malignant cells, allowing for cancer identification and then assessing patient cohorts for prognostic and predictive value. Typically, CTC identification relies on immunofluorescent staining assessed as absent/present, which is somewhat subjective and limited in its ability to characterize these cells. …
Lineage-Specific Differences In The Gp120 Inner Domain Layer 3 Of Human And Simian Immunodeficiency Viruses, Shilei Ding, Halima Medjahed, Jérémie Prévost, Mathieu Coutu, Shi-Hua Xiang, Andrés Finzi
Lineage-Specific Differences In The Gp120 Inner Domain Layer 3 Of Human And Simian Immunodeficiency Viruses, Shilei Ding, Halima Medjahed, Jérémie Prévost, Mathieu Coutu, Shi-Hua Xiang, Andrés Finzi
Nebraska Center for Virology: Faculty Publications
Binding of HIV-1 and SIV gp120 exterior envelope glycoprotein to CD4 triggers conformational changes in gp120 that promote its interaction with one of the chemokine receptors, usually CCR5, ultimately leading to gp41-mediated virus-cell membrane fusion and entry. We previously described that topological Layers (Layer 1, Layer 2 and Layer 3) in the gp120 inner domain contribute to gp120-trimer association in the unliganded state but also help secure CD4 binding. Relative to Layer 1 of HIV-1 gp120, the SIVmac239 gp120 Layer 1 plays a more prominent role in maintaining gp120-trimer association but is minimally involved in promoting CD4 binding, which could …
Chronic Pancreatitis, Pain, And Anxiety In An Alcohol And High Fat Mouse Model, Tiffanie Clinkinbeard
Chronic Pancreatitis, Pain, And Anxiety In An Alcohol And High Fat Mouse Model, Tiffanie Clinkinbeard
Theses and Dissertations--Gerontology
Homeodynamic space (HDS) shrinks as vulnerability increases with aging and repeated damage to the cells. HDS is lost in alcoholic pancreatitis patients due to overconsumption of alcohol, smoking, and high fat diets. Etiologically relevant animal models for study of chronic pancreatitis (CP) are needed. In order to begin filling this gap a central purpose of this dissertation research was to examine relationships between the alcohol and high fat diet (AHF) and pancreatitis with attention to hypersensitivity and anxiety-like behaviors. The AHF diet induced pancreatitis described here etiologically mimics human risk factors of AHF consumption for advancement to alcoholic CP.
In …
Il-15 Mediates Mitochondrial Activity Through A Ppar𝛿-Dependent-Ppar𝛼-Independent Mechanism In Skeletal Muscle Cells, Shantaé M. Thornton, James E. Krolopp, Marcia J. Abbott
Il-15 Mediates Mitochondrial Activity Through A Ppar𝛿-Dependent-Ppar𝛼-Independent Mechanism In Skeletal Muscle Cells, Shantaé M. Thornton, James E. Krolopp, Marcia J. Abbott
Health Sciences and Kinesiology Faculty Articles
Molecular mediators of metabolic processes, to increase energy expenditure, have become a focus for therapies of obesity. The discovery of cytokines secreted from the skeletal muscle (SKM), termed “myokines,” has garnered attention due to their positive effects on metabolic processes. Interleukin-15 (IL-15) is a myokine that has numerous positive metabolic effects and is linked to the PPAR family of mitochondrial regulators. Here, we aimed to determine the importance of PPAR𝛼 and/or PPAR𝛿 as targets of IL-15 signaling. C2C12 SKM cells were differentiated for 6 days and treated every other day with IL-15 (100 ng/mL), a PPAR𝛼 inhibitor (GW-6471), a PPAR𝛿 …
Giant Chloroviruses: Five Easy Questions, James L. Van Etten, David Dunigan
Giant Chloroviruses: Five Easy Questions, James L. Van Etten, David Dunigan
Nebraska Center for Virology: Faculty Publications
Chloroviruses are large, icosahedral, dsDNA-containing viruses that replicate in certain unicellular, chlorella-like green algae [1,2]. They exist in freshwater throughout the world with titers as high as thousands of plaque-forming units (PFU) per ml of indigenous water although titers are typically 1–100 PFU/ml. Titers fluctuate during the year with the highest titers typically occurring in the spring and late fall. Known chlorovirus hosts, which are normally symbionts and are often referred to as zoochlorellae, are associated with either the protozoan Paramecium bursaria (Fig 1A), the coelenterate Hydra viridis, or the heliozoan Acanthocystis turfacea. Zoochlorellae are resistant to viruses …
Genetic Barrier To Direct Acting Antivirals In Hcv Sequences Deposited In The European Databank, Dimas Alexandre Kliemann, Cristiane Valle Tovo, Ana Beatriz Gorini Da Veiga, André Luiz Machado, John T. West
Genetic Barrier To Direct Acting Antivirals In Hcv Sequences Deposited In The European Databank, Dimas Alexandre Kliemann, Cristiane Valle Tovo, Ana Beatriz Gorini Da Veiga, André Luiz Machado, John T. West
Nebraska Center for Virology: Faculty Publications
Background & Aims: Development of resistance results from mutations in the viral genome, and the presence of selective drug pressure leads to the emergence of a resistant virus population. The aim of this study was to analyze the impact of genetic variability on the genetic barrier to drug resistance to DAAs.
Methods: The genetic barrier was quantified based on the number and type of nucleotide mutations required to impart resistance, considering full-length HCV NS3, NS5A and NS5B regions segregated by genotype into subtypes 1a, 1b, 2a, 2b and 3a. This study analyzed 789 NS3 sequences, 708 sequences and 536 NS5B …
Kaposi’S Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation Primary-Response Gene 88 (Myd88) Expression Via Modulation Of Its Rna, Amy Lingel, Erica Ehlers, Qianli Wang, Mingxia Cao, Charles Wood, Rongtuan Lin, Luwen Zhang
Kaposi’S Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation Primary-Response Gene 88 (Myd88) Expression Via Modulation Of Its Rna, Amy Lingel, Erica Ehlers, Qianli Wang, Mingxia Cao, Charles Wood, Rongtuan Lin, Luwen Zhang
Nebraska Center for Virology: Faculty Publications
Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Interleukin 1 (IL-1) is a major mediator for inflammation and plays an important role in both innate and adaptive immunity. Myeloid differentiation primary response gene 88 (MyD88) is an essential adaptor molecule for IL-1 as well as most Toll-like receptor signaling. In this study, we identified a novel mechanism by which KSHV interferes with host inflammation and immunity. KSHV RTA specifically reduces the steady-state protein levels of …
Nf45 And Nf90 Bind Hiv-1 Rna And Modulate Hiv Gene Expression, Yan Li, Michael Belshan
Nf45 And Nf90 Bind Hiv-1 Rna And Modulate Hiv Gene Expression, Yan Li, Michael Belshan
Nebraska Center for Virology: Faculty Publications
A previous proteomic screen in our laboratory identified nuclear factor 45 (NF45) and nuclear factor 90 (NF90) as potential cellular factors involved in human immunodeficiency virus type 1 (HIV-1) replication. Both are RNA binding proteins that regulate gene expression; and NF90 has been shown to regulate the expression of cyclin T1 which is required for Tat-dependent trans-activation of viral gene expression. In this study the roles of NF45 and NF90 in HIV replication were investigated through overexpression studies. Ectopic expression of either factor potentiated HIV infection, gene expression, and virus production. Deletion of the RNA binding domains of NF45 …
Mucosal Vaccination By Adenoviruses Displaying Reovirus Sigma 1, Eric A. Weaver, Zenaido T. Camacho, Matthew L. Hillestad, Catherine M. Crosby, Mallory A. Turner, Adam J. Guenzel, Hind J. Fadel, George T. Mercier, Michael A. Barry
Mucosal Vaccination By Adenoviruses Displaying Reovirus Sigma 1, Eric A. Weaver, Zenaido T. Camacho, Matthew L. Hillestad, Catherine M. Crosby, Mallory A. Turner, Adam J. Guenzel, Hind J. Fadel, George T. Mercier, Michael A. Barry
Nebraska Center for Virology: Faculty Publications
We previously developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but had 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generated stronger T cell responses than Ad5 when used for mucosal immunization. New Ad5- fiber-sigma vectors were generated here by varying the number of fiber β-spiral shaft repeats (R) fused between fiber tail and the sigma. Ad5 virions encoding R3, R14, and R20 chimeras were rescued. Increasing chimera length led to their decreasing encapsidation of these proteins in the virions. …
Large Genomic Differences Between Moraxella Bovoculi Isolates Acquired From The Eyes Of Cattle With Infectious Bovine Keratoconjunctivitis Versus The Deep Nasopharynx Of Asymptomatic Cattle, Aaron M. Dickey, John D. Loy, James L. Bono, Timonthy P. L. Smith, Mike D. Apley, Brian V. Lubbers, Keith D. Dedonder, Sarah F. Capik, Robert L. Larson, Brad J. White, Jochen Blom, Carol G. Chitko-Mckown, Michael L. Clawson
Large Genomic Differences Between Moraxella Bovoculi Isolates Acquired From The Eyes Of Cattle With Infectious Bovine Keratoconjunctivitis Versus The Deep Nasopharynx Of Asymptomatic Cattle, Aaron M. Dickey, John D. Loy, James L. Bono, Timonthy P. L. Smith, Mike D. Apley, Brian V. Lubbers, Keith D. Dedonder, Sarah F. Capik, Robert L. Larson, Brad J. White, Jochen Blom, Carol G. Chitko-Mckown, Michael L. Clawson
School of Veterinary and Biomedical Sciences: Faculty Publications
Moraxella bovoculi is a recently described bacterium that is associated with infectious bovine keratoconjunctivitis (IBK) or “pinkeye” in cattle. In this study, closed circularized genomes were generated for seven M. bovoculi isolates: three that originated from the eyes of clinical IBK bovine cases and four from the deep nasopharynx of asymptomatic cattle. Isolates that originated from the eyes of IBK cases profoundly differed from those that originated from the nasopharynx of asymptomatic cattle in genome structure, gene content and polymorphism diversity and consequently placed into two distinct phylogenetic groups. These results suggest that there are genetically distinct strains of M. …
Presence Of Pathogenic Escherichia Coli Is Correlated With Bacterial Community Diversity And Composition On Pre-Harvest Cattle Hides, Jessica Chopyk, Ryan M. Moore, Zachary Dispirito, Zachary R. Stromberg, Gentry L. Lewis, David G. Renter, Natalia Cernicchiaro, Rodney A. Moxley, K. Eric Wommack
Presence Of Pathogenic Escherichia Coli Is Correlated With Bacterial Community Diversity And Composition On Pre-Harvest Cattle Hides, Jessica Chopyk, Ryan M. Moore, Zachary Dispirito, Zachary R. Stromberg, Gentry L. Lewis, David G. Renter, Natalia Cernicchiaro, Rodney A. Moxley, K. Eric Wommack
School of Veterinary and Biomedical Sciences: Faculty Publications
Background: Since 1982, specific serotypes of Shiga toxin-producing Escherichia coli (STEC) have been recognized as significant foodborne pathogens acquired from contaminated beef and, more recently, other food products. Cattle are the major reservoir hosts of these organisms, and while there have been advancements in food safety practices and industry standards, STEC still remains prevalent within beef cattle operations with cattle hides implicated as major sources of carcass contamination. To investigate whether the composition of hide-specific microbial communities are associated with STEC prevalence, 16S ribosomal RNA (rRNA) bacterial community profiles were obtained from hide and fecal samples collected from a large …
Prevalence And Level Of Enterohemorrhagic Escherichia Coli In Culled Dairy Cows At Harvest, Zachary R. Stromberg, Gentry L. Lewis, Sharif S. Aly, Terry W. Lehenbauer, Joseph M. Bosilevac, Natalia Cernicchiaro, Rodney A. Moxley
Prevalence And Level Of Enterohemorrhagic Escherichia Coli In Culled Dairy Cows At Harvest, Zachary R. Stromberg, Gentry L. Lewis, Sharif S. Aly, Terry W. Lehenbauer, Joseph M. Bosilevac, Natalia Cernicchiaro, Rodney A. Moxley
School of Veterinary and Biomedical Sciences: Faculty Publications
The primary objective of this study was to determine the prevalence and level of enterohemorrhagic Escherichia coli (EHEC) O26, O45, O103, O111, O121, and O145 (collectively EHEC-6) plus EHEC O157 in fecal, hide, and preintervention carcass surface samples from culled dairy cows. Matched samples (n=300) were collected from 100 cows at harvest and tested by a culture-based method and two molecular methods: NeoSEEK STEC (NS) and Atlas STEC EG2 Combo. Both the culture and NS methods can be used to discriminate among the seven EHEC types (EHEC-7), from which the cumulative prevalence was inferred, whereas the Atlas method can discriminate …
Recapitulating Cross-Species Transmission Of Sivcpz To Humans Using Humanized-Blt Mice, Zhe Yuan, Guobin Kang, Fangrui Ma, Wuxun Lu, Wenjin Fan, Christine M. Fennessey, Brandon F. Keele, Qingsheng Li
Recapitulating Cross-Species Transmission Of Sivcpz To Humans Using Humanized-Blt Mice, Zhe Yuan, Guobin Kang, Fangrui Ma, Wuxun Lu, Wenjin Fan, Christine M. Fennessey, Brandon F. Keele, Qingsheng Li
Nebraska Center for Virology: Faculty Publications
The origins of HIV-1 have been widely accepted to be the consequence of simian immunodeficiency viruses from wild chimpanzees (SIVcpz) crossing over to humans. However, there has not been any in vivo study of SIVcpz infection of humans. Also, it remains largely unknown why only specific SIVcpz strains have achieved cross-species transmission and what transmission risk might exist for those SIVcpz strains that have not been found to infect humans. Closing this knowledge gap is essential for better understanding cross-species transmission and predicting the likelihood of additional cross-species transmissions of SIV into humans. Here we show hu-BLT mice are susceptible …
High Glucose Induces Reactivation Of Latent Kaposi’S Sarcoma-Associated Herpesvirus, Fengchun Ye, Yan Zeng, Jingfeng Sha, Tiffany Jones, Kurt Kuhne, Charles Wood, Shou-Jiang Gao
High Glucose Induces Reactivation Of Latent Kaposi’S Sarcoma-Associated Herpesvirus, Fengchun Ye, Yan Zeng, Jingfeng Sha, Tiffany Jones, Kurt Kuhne, Charles Wood, Shou-Jiang Gao
Nebraska Center for Virology: Faculty Publications
High prevalence of Kaposi’s sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological condition of diabetes contributes to KS development. We found elevated levels of viral lytic gene expression when Kaposi’s sarcoma-associated herpesvirus (KSHV) infected cells were cultured in high glucose medium. To demonstrate the association between high glucose and KSHV replication, we xeno29
grafted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high …
Persistent Low-Level Replication Of Sivδnef Drives Maturation Of Antibody And Cd8 T Cell Responses To Induce Protective Immunity Against Vaginal Siv Infection, Sama Adnan, R. Keith Reeves, Jacqueline Gillis, Fay E. Wong, Yi Yu, Jeremy V. Camp, Qingsheng Li, Michelle Connole, Yuan Li, Michael Piatak Jr., Jeffrey D. Lifson, Wenjun Li, Brandon F. Keele, Pamela A. Kozlowski, Ronald C. Desrosiers, Ashley T. Haase, R. Paul Johnson
Persistent Low-Level Replication Of Sivδnef Drives Maturation Of Antibody And Cd8 T Cell Responses To Induce Protective Immunity Against Vaginal Siv Infection, Sama Adnan, R. Keith Reeves, Jacqueline Gillis, Fay E. Wong, Yi Yu, Jeremy V. Camp, Qingsheng Li, Michelle Connole, Yuan Li, Michael Piatak Jr., Jeffrey D. Lifson, Wenjun Li, Brandon F. Keele, Pamela A. Kozlowski, Ronald C. Desrosiers, Ashley T. Haase, R. Paul Johnson
Nebraska Center for Virology: Faculty Publications
Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef …
Local Corticotropin Releasing Hormone (Crh) Signals To Its Receptor Crhr1 During Postnatal Development Of The Mouse Olfactory Bulb, Isabella Garcia, Paramjit K Bhullar, Burak Tepe, Joshua Ortiz-Guzman, Longwen Huang, Alexander M Herman, Lesley Chaboub, Benjamin Deneen, Nicholas J Justice, Benjamin R Arenkiel
Local Corticotropin Releasing Hormone (Crh) Signals To Its Receptor Crhr1 During Postnatal Development Of The Mouse Olfactory Bulb, Isabella Garcia, Paramjit K Bhullar, Burak Tepe, Joshua Ortiz-Guzman, Longwen Huang, Alexander M Herman, Lesley Chaboub, Benjamin Deneen, Nicholas J Justice, Benjamin R Arenkiel
Faculty, Staff and Students Publications
Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related …
Complete Genome Sequence Of Highly Virulent Porcine Reproductive And Respiratory Syndrome Virus Variants That Recently Emerged In The United States, Aspen M. Workman, Timothy P.L. Smith, Fernando A. Osorio, Hiep L.X. Vu
Complete Genome Sequence Of Highly Virulent Porcine Reproductive And Respiratory Syndrome Virus Variants That Recently Emerged In The United States, Aspen M. Workman, Timothy P.L. Smith, Fernando A. Osorio, Hiep L.X. Vu
Nebraska Center for Virology: Faculty Publications
A recent outbreak of particularly virulent disease caused by porcine reproductive and respiratory syndrome virus has occurred in swine herds across the United States. We report here the complete genome sequence of eight viral isolates from four Nebraska herds experiencing an outbreak of severe disease in 2016.
Domain I Of The 5′ Non-Translated Genomic Region In Coxsackievirus B3 Rna Is Not Required For Productive Replication, L. Jaramillo, S. Smithee, S. Tracy, N. M. Chapman
Domain I Of The 5′ Non-Translated Genomic Region In Coxsackievirus B3 Rna Is Not Required For Productive Replication, L. Jaramillo, S. Smithee, S. Tracy, N. M. Chapman
Nebraska Center for Virology: Faculty Publications
Domain I is a cloverleaf-like secondary structure at the 5′ termini of all enterovirus genomes, comprising part of a cis-acting replication element essential for efficient enteroviral replication. 5′ genomic terminal deletions up to as much as 55% of domain I can occur without lethality following coxsackie B virus infections. We report here that the entire CVB structural domain I can be deleted without lethality.
Reversion To Wildtype Of A Mutated And Nonfunctional Coxsackievirus B3cre(2c), Shane Smithee, Steven Tracy, Nora M. Chapman
Reversion To Wildtype Of A Mutated And Nonfunctional Coxsackievirus B3cre(2c), Shane Smithee, Steven Tracy, Nora M. Chapman
Nebraska Center for Virology: Faculty Publications
The cis-acting replication element (CRE) in the 2C protein coding region [CRE(2C)] of enteroviruses (EV) facilitates the addition of two uridine residues (uridylylation) onto the virus-encoded protein VPg inorder for it to serve as the RNA replication primer. We demonstrated that coxsackievirus B3 (CVB3) is replication competent in the absence of a native (uridylylating) CRE(2C) and also demonstrated that lackof a functional CRE(2C) led to generation of 5’ terminal genomic deletions in the CVB3 CRE-knock-out (CVB3-CKO) population. We asked whether reversion of the mutated CRE(2C) occurred, thus permitting sustained replication, and when were 5’ terminal deletions generated during replication. Virions …
Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses, Catherine M. Crosby, William E. Matchett, Stephanie S. Anguiano-Zarate, Christopher A. Parks, Eric A. Weaver, Larry R. Pease, Richard J. Webby, Michael A. Barry
Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses, Catherine M. Crosby, William E. Matchett, Stephanie S. Anguiano-Zarate, Christopher A. Parks, Eric A. Weaver, Larry R. Pease, Richard J. Webby, Michael A. Barry
Nebraska Center for Virology: Faculty Publications
Head-to-head comparisons of conventional influenza vaccines with ade- novirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we de- veloped “single-cycle” adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than …
Autoimmunity In Picornavirus Infections, Chandirasegara Massilamany, Andreas Koenig, Jay Reddy, Sally Huber, Iwona Buskiewicz
Autoimmunity In Picornavirus Infections, Chandirasegara Massilamany, Andreas Koenig, Jay Reddy, Sally Huber, Iwona Buskiewicz
School of Veterinary and Biomedical Sciences: Faculty Publications
Enteroviruses are small, non-enveloped, positive-sense singlestrand RNA viruses, and are ubiquitously found throughout the world. These viruses usually cause asymptomatic or mild febrile illnesses, but have a propensity to induce severe diseases including type 1 diabetes and pancreatitis, paralysis and neuroinflammatory disease, myocarditis, or hepatitis. This pathogenicity may result from induction of autoimmunity to organ-specific antigens. While enterovirus-triggered autoimmunity can arise from multiple mechanisms including antigenic mimicry and release of sequestered antigens, the recent demonstration of T cells expressing dual T cell receptors arising as a natural consequence of Theiler’s virus infection is the first demonstration of this autoimmune mechanism.
Genome-Wide Search For Host Association Factors During Ovine Progressive Pneumonia Virus Infection, Jesse Thompson, Fangrui Ma, Meghan Quinn, Shi-Hua Xiang
Genome-Wide Search For Host Association Factors During Ovine Progressive Pneumonia Virus Infection, Jesse Thompson, Fangrui Ma, Meghan Quinn, Shi-Hua Xiang
School of Veterinary and Biomedical Sciences: Faculty Publications
Ovine progressive pneumonia virus (OPPV) is an important virus that causes serious diseases in sheep and goats with a prevalence of 36% in the USA. Although OPPV was discovered more than half of a century ago, little is known about the infection and pathogenesis of this virus. In this report, we used RNA-seq technology to conduct a genome-wide probe for cellular factors that are associated with OPPV infection. A total of approximately 22,000 goat host genes were detected of which 657 were found to have been significantly up-regulated and 889 down-regulated at 12 hours post-infection. In addition to previously known …
Guidelines For The Use And Interpretation Of Assays For Monitoring Autophagy (3rd Edition), Daniel J. Klionsky, Rodrigo Franco, More Than 2,000 Co-Authors
Guidelines For The Use And Interpretation Of Assays For Monitoring Autophagy (3rd Edition), Daniel J. Klionsky, Rodrigo Franco, More Than 2,000 Co-Authors
School of Veterinary and Biomedical Sciences: Faculty Publications
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.
For example, a key point that needs to be emphasized is that …
From Crystal Structure Of Α-Conotoxin Gic In Complex With Ac-Achbp To Molecular Determinants Of Its High Selectivity For Α3Β2 Nachr, Bo Lin, Manyu Xu, Xiaopeng Zhu, Yong Wu, Xi Liu, Dongting Zhangsun, Yuanyan Hu, Shi-Hua Xiang, Igor E. Kasheverov, Victor I. Tsetlin, Xinquan Wang, Sulan Luo
From Crystal Structure Of Α-Conotoxin Gic In Complex With Ac-Achbp To Molecular Determinants Of Its High Selectivity For Α3Β2 Nachr, Bo Lin, Manyu Xu, Xiaopeng Zhu, Yong Wu, Xi Liu, Dongting Zhangsun, Yuanyan Hu, Shi-Hua Xiang, Igor E. Kasheverov, Victor I. Tsetlin, Xinquan Wang, Sulan Luo
School of Veterinary and Biomedical Sciences: Faculty Publications
Acetylcholine binding proteins (AChBPs) are unique spatial homologs of the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs), and they reproduce some pharmacological properties of nAChRs. X-ray crystal structures of AСhBP in complex with α-conotoxins provide important insights into the interactions of α-conotoxins with distinct nAChR subtypes. Although considerable efforts have been made to understand why α-conotoxin GIC is strongly selective for α3β2 nAChR, this question has not yet been solved. Here we present the structure of α-conotoxin GIC in complex with Aplysia californica AChBP (Ac-AChBP) at a resolution of 2.1 Å. Based on this co-crystal structure complemented with molecular docking …
From Crystal Structure Of Α-Conotoxin Gic In Complex With Ac-Achbp To Molecular Determinants Of Its High Selectivity For Α3Β2 Nachr, Bo Lin, Manyu Xu, Xiaopeng Zhu, Yong Wu, Xi Liu, Dongting Zhangsun, Yuanyan Hu, Shi-Hua Xiang, Igor E. Kasheverov, Victor I. Tsetlin, Xianquan Wang, Sulan Luo
From Crystal Structure Of Α-Conotoxin Gic In Complex With Ac-Achbp To Molecular Determinants Of Its High Selectivity For Α3Β2 Nachr, Bo Lin, Manyu Xu, Xiaopeng Zhu, Yong Wu, Xi Liu, Dongting Zhangsun, Yuanyan Hu, Shi-Hua Xiang, Igor E. Kasheverov, Victor I. Tsetlin, Xianquan Wang, Sulan Luo
School of Veterinary and Biomedical Sciences: Faculty Publications
Acetylcholine binding proteins (AChBPs) are unique spatial homologs of the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs), and they reproduce some pharmacological properties of nAChRs. X-ray crystal structures of AСhBP in complex with α-conotoxins provide important insights into the interactions of α-conotoxins with distinct nAChR subtypes. Although considerable efforts have been made to understand why α-conotoxin GIC is strongly selective for α3β2 nAChR, this question has not yet been solved. Here we present the structure of α-conotoxin GIC in complex with Aplysia californica AChBP (Ac-AChBP) at a resolution of 2.1 Å. Based on this co-crystal structure complemented with molecular docking …
A Synthetic Porcine Reproductive And Respiratory Syndrome Unprecedented Levels Of Heterologous Protection, Hiep Vu, Fangrui Ma, William W. Laegreid, Asit K. Pattnaik, David Steffen, Alan R. Doster, Fernando A. Osorio
A Synthetic Porcine Reproductive And Respiratory Syndrome Unprecedented Levels Of Heterologous Protection, Hiep Vu, Fangrui Ma, William W. Laegreid, Asit K. Pattnaik, David Steffen, Alan R. Doster, Fernando A. Osorio
School of Veterinary and Biomedical Sciences: Faculty Publications
Current vaccines do not provide sufficient levels of protection against divergent porcine reproductive and respiratory syndrome virus (PRRSV) strains circulating in the field, mainly due to the substantial variation of the viral genome. We describe here a novel approach to generate a PRRSV vaccine candidate that could confer unprecedented levels of heterologous protection against divergent PRRSV isolates. Using a set of 59 non-redundant, full genome sequences of type-2 PRRSV, a consensus genome (designated as PRRSV-CON) was these 59 PRRSV full genome sequences, followed by selecting the most common nucleotide found at each position of the alignment. Next, the synthetic PRRSV-CON …
Overview Of Rhabdo- And Filoviruses, Asit K. Pattnaik, Michael A. Whitt
Overview Of Rhabdo- And Filoviruses, Asit K. Pattnaik, Michael A. Whitt
School of Veterinary and Biomedical Sciences: Faculty Publications
Enveloped viruses with a negative-sense, single-stranded monopartite RNA genome have been classified into the order Mononegavirales. Five families of viruses that constitute the order are: Rhabdoviridae, Filoviridae, Paramyxoviridae, Bornaviridae and Nyamiviridae. Members of these families possess a helical nucleocapsid core containing the viral genome and a host-derived lipid envelope containing viral proteins. This introductory chapter provides a brief overview of the Rhabdoviridae and the Filoviridae, the two families of viruses that are the subject of this book. Many members of these two families are highly significant human and animal pathogens. The rationale and goal of the book is to …