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Full-Text Articles in Medicine and Health Sciences

Glutaredoxin 2 (Grx2) Knockout Increases Sensitivity To Oxidative Stress In Mouse Lens Epithelial Cells, Hongli Wu, Liren Lin, Frank Giblin, Ye-Sheh Ho, Marjorie F. Lou Dec 2012

Glutaredoxin 2 (Grx2) Knockout Increases Sensitivity To Oxidative Stress In Mouse Lens Epithelial Cells, Hongli Wu, Liren Lin, Frank Giblin, Ye-Sheh Ho, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin belongs to the oxidoreductase family with cytosolic glutaredoxin 1 (Grx1) and mitochondrial gluraredoxin 2 (Grx2) isoforms. Of the two isozymes, the function of Grx2 is not well understood. This paper studied the effect of Grx2 deletion on cellular function using primary lens epithelial cell cultures isolated from Grx2 gene knockout (KO) and wild type (WT) mice. We found that both cell types showed similar growth patterns and morphology, and comparable mitochondrial glutathione pool and complex I activity. Cells with deleted Grx2 did not show affected Grx1 or thioredoxin (Trx) expression but exhibited high sensitivity to oxidative stress. Under treatment …


Medical Nutrition Therapy Provided To Adult Hematopoietic Stem Cell Transplantation Patients, Mary G. Habschmidt, Cheryl A. Bacon, Mary B. Gregoire, Heather E. Rasmussen Oct 2012

Medical Nutrition Therapy Provided To Adult Hematopoietic Stem Cell Transplantation Patients, Mary G. Habschmidt, Cheryl A. Bacon, Mary B. Gregoire, Heather E. Rasmussen

Department of Nutrition and Health Sciences: Faculty Publications

This study explored the current medical nutrition therapy (MNT) provided to adult patients undergoing hematopoietic stem cell transplantation (HSCT) and examined the current and desired role of registered dietitians (RDs) in providing MNT. A total of 60 RDs (57% response rate) responded to an electronic questionnaire. Descriptive statistics and χ2 analyses (SPSS, version 18) were used. Results revealed the primary form of diet was oral, and for patients on nutrition support, parenteral nutrition (PN) was used more frequently (16%–31%) than enteral nutrition (EN) (5%–9%; P ≤ .05). Nutrition support decisions were based on patients’ individualized needs rather than established …


Ultraviolet Radiation–Induced Cataract In Mice: The Effect Of Age And The Potential Biochemical Mechanism, Jie Zhang, Hong Yan, Stefan Lofgren, Xiaoli Tian, Marjorie F. Lou Sep 2012

Ultraviolet Radiation–Induced Cataract In Mice: The Effect Of Age And The Potential Biochemical Mechanism, Jie Zhang, Hong Yan, Stefan Lofgren, Xiaoli Tian, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. To study the effect of age on the morphologic and biochemical alterations induced by in vivo exposure of ultraviolet radiation (UV).

METHODS. Young and old C57BL/6 mice were exposed to broadband UVBþUVA and euthanized after 2 days. Another batch of UV-exposed young mice was monitored for changes after 1, 2, 4, and 8 days. Age-matched nonexposed mice served as controls. Lens changes were documented in vivo by slit-lamp biomicroscopy and dark field microscopy photographs ex vivo. Lens homogenates were analyzed for glutathione (GSH) level, and the activities of thioredoxin (Trx), thioltransferase (TTase), and glyceraldehyde-3-phosphate dehydrogenase (G3PD). Glutathionylated lens proteins …


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 Aug 2012

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 …


Melanopsin Mediates Retrograde Visual Signaling In The Retina, Dao-Qi Zhang, Michael A. Belenky, Patricia J. Sollars, Gary E. Pickard, Douglas G. Mcmahon Aug 2012

Melanopsin Mediates Retrograde Visual Signaling In The Retina, Dao-Qi Zhang, Michael A. Belenky, Patricia J. Sollars, Gary E. Pickard, Douglas G. Mcmahon

School of Veterinary and Biomedical Sciences: Faculty Publications

The canonical flow of visual signals proceeds from outer to inner retina (photoreceptors→bipolar cells→ganglion cells). However, melanopsin-expressing ganglion cells are photosensitive and functional sustained light signaling to retinal dopaminergic interneurons persists in the absence of rods and cones. Here we show that the sustained-type light response of retinal dopamine neurons requires melanopsin and that the response is mediated by AMPA-type glutamate receptors, defining a retrograde retinal visual signaling pathway that fully reverses the usual flow of light signals in retinal circuits.


Harvesting Murine Alveolar Macrophages And Evaluating Cellular Activation Induced By Polyanhydride Nanoparticles, Ana V. Chavez-Santoscoy, Lucas M. Huntlimer, Amanda E. Ramer-Tait, Michael J. Wannemeuhler, Balaji Narasimhan Jun 2012

Harvesting Murine Alveolar Macrophages And Evaluating Cellular Activation Induced By Polyanhydride Nanoparticles, Ana V. Chavez-Santoscoy, Lucas M. Huntlimer, Amanda E. Ramer-Tait, Michael J. Wannemeuhler, Balaji Narasimhan

Amanda Ramer-Tait Publications

Biodegradable nanoparticles have emerged as a versatile platform for the design and implementation of new intranasal vaccines against respiratory infectious diseases. Specifically, polyanhydride nanoparticles composed of the aliphatic sebacic acid (SA), the aromatic 1,6-bis(p-carboxyphenoxy)hexane (CPH), or the amphiphilic 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) display unique bulk and surface erosion kinetics1,2 and can be exploited to slowly release functional biomolecules (e.g., protein antigens, immunoglobulins, etc.) in vivo3,4,5. These nanoparticles also possess intrinsic adjuvant activity, making them an excellent choice for a vaccine delivery platform6,7,8.

In order to elucidate the mechanisms governing the activation of innate …


Chemistry-Dependent Adsorption Of Serum Proteins Onto Polyanhydride Microparticles Differentially Influences Dendritic Cell Uptake And Activation, Brenda R. Carrillo-Conde, Amanda E. Ramer-Tait, Michael J. Wannemeuhler, Balaji Narasimhan Jun 2012

Chemistry-Dependent Adsorption Of Serum Proteins Onto Polyanhydride Microparticles Differentially Influences Dendritic Cell Uptake And Activation, Brenda R. Carrillo-Conde, Amanda E. Ramer-Tait, Michael J. Wannemeuhler, Balaji Narasimhan

Amanda Ramer-Tait Publications

The delivery of antigen-loaded microparticles to dendritic cells (DCs) may benefit from surface optimization of the microparticles themselves, thereby exploiting the material properties and introducing signals that mimic pathogens. Following in vivo administration microparticle surface characteristics are likely to be significantly modified as proteins are quickly adsorbed onto their surface. In this work we describe the chemistry-dependent serum protein adsorption patterns on polyanhydride particles and the implications for their molecular interactions with DCs. The enhanced expression of MHC II and CD40 on DCs after incubation with amphiphilic polyanhydride particles, and the increased secretion of IL-6, TNF-α, and IL-12p40 by hydrophobic …


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 Apr 2012

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 …


Tailoring The Immune Response By Targeting C-Type Lectin Receptors On Alveolar Macrophages Using “Pathogen-Like” Amphiphilic Polyanhydride Nanoparticles, Ana V. Chavez-Santicoy, Rajarshi Roychoudhury, Nicola L.B. Pohl, Michael J. Wannemeuhler, Balaji Narasimhan, Amanda E. Ramer-Tait Apr 2012

Tailoring The Immune Response By Targeting C-Type Lectin Receptors On Alveolar Macrophages Using “Pathogen-Like” Amphiphilic Polyanhydride Nanoparticles, Ana V. Chavez-Santicoy, Rajarshi Roychoudhury, Nicola L.B. Pohl, Michael J. Wannemeuhler, Balaji Narasimhan, Amanda E. Ramer-Tait

Amanda Ramer-Tait Publications

C-type lectin receptors (CLRs) offer unique advantages for tailoring immune responses. Engagement of CLRs regulates antigen presenting cell (APC) activation and promotes delivery of antigens to specific intracellular compartments inside APCs for efficient processing and presentation. In these studies, we have designed an approach for targeted antigen delivery by decorating the surface of polyanhydride nanoparticles with specific carbohydrates to provide pathogen-like properties. Two conserved carbohydrate structures often found on the surface of respiratory pathogens, galactose and di-mannose, were used to functionalize the surface of polyanhydride nanoparticles and target CLRs on alveolar macrophages (AMϕ), a principle respiratory tract APC. Co-culture of …


Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry Mar 2012

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 Mar 2012

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 Mar 2012

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 …


Copper–Zinc Superoxide Dismutase-Deficient Mice Show Increased Susceptibility To Experimental Autoimmune Encephalomyelitis Induced With Myelin Oligodendrocyte Glycoprotein 35–55, Chandirasegara Massilamany, Arunakumar Gangaplara, Heejeong Kim, Charlotte Standord, Govardhan Rathnaiah, David Steffen, Jaekwon Lee, Jay Reddy Jan 2012

Copper–Zinc Superoxide Dismutase-Deficient Mice Show Increased Susceptibility To Experimental Autoimmune Encephalomyelitis Induced With Myelin Oligodendrocyte Glycoprotein 35–55, Chandirasegara Massilamany, Arunakumar Gangaplara, Heejeong Kim, Charlotte Standord, Govardhan Rathnaiah, David Steffen, Jaekwon Lee, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

In this report, we have addressed the role of copper–zinc superoxide dismutase (SOD1) deficiency in the mediation of central nervous system autoimmunity. We demonstrate that SOD1-deficient C57Bl/6 mice develop more severe autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein (MOG) 35–55, compared with wild type mice. This alteration in the disease phenotype was not due to aberrant expansion of MOG-specific T cells nor their ability to produce inflammatory cytokines; rather lymphocytes generated in SOD1-deficient mice were more prone to spontaneous cell death when compared with their wild type littermate controls. The data point to a role for SOD1 in the maintenance …


Rhodotorula Minuta Fungemia In A Ewe Lamb, C G. Chitko-Mckown, K A. Leymaster, M. P. Heaton, D D. Griffin, J K. Veatch, S A. Jones, M. L. Clawson Jan 2012

Rhodotorula Minuta Fungemia In A Ewe Lamb, C G. Chitko-Mckown, K A. Leymaster, M. P. Heaton, D D. Griffin, J K. Veatch, S A. Jones, M. L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

An 8-month-old crossbred ewe, normal upon physical examination, was humanely euthanized for tissue collection. After approximately 3 weeks in tissue culture, fungi began budding out of cells obtained from the choroid plexus. After an additional 3 weeks, budding was observed in kidney cell cultures and eventually in monocyte cultures as well. Serum from the lamb was submitted to the Veterinary Diagnostic Laboratory at Colorado State University for fungal diagnosis and was found negative for Aspergillus, Blastomyces, Coccidioidomycosis and Histoplasmosis. DNA was isolated from fungi collected from tissue culture supernatants and used in a set of pan-fungal PCR assays with DNA …


Identification Of Amino Acid Residues Important For Anti-Ifn Activity Of Porcine Reproductive And Respiratory Syndrome Virus Non-Structural Protein 1, Lalit Beura, Sakthivel Subramaniam, Hiep Vu, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio Jan 2012

Identification Of Amino Acid Residues Important For Anti-Ifn Activity Of Porcine Reproductive And Respiratory Syndrome Virus Non-Structural Protein 1, Lalit Beura, Sakthivel Subramaniam, Hiep Vu, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

The non-structural protein 1 (nsp1) of porcine reproductive and respiratory syndrome virus is partly responsible for inhibition of type I interferon (IFN) response by the infected host. By performing alanine-scanning mutagenesis, we have identified amino acid residues in nsp1α and nsp1β~ (the proteolytic products of nsp1) that when substituted with alanine(s) exhibited significant relief of IFNsuppression. A mutant virus (16-SA, in which residues 16-20 of nsp1β were substituted with alanines) encoding mutant nsp1β recovered from infectious cDNA clone was shown to be attenuated for growth in vitro and induced significantly higher amount of type I IFN transcripts in infected macrophages. …


A Single Amino Acid Change Resulting In Loss Of Fluorescence Of Egfp In A Viral Fusion Protein Confers Fitness And Growth Advantage To The Recombinant Vesicular Stomatitis Virus, Phat X. Dinh, Debasis Panda, Phani B. Das, Subash C. Das, Anshuman Das, Asit K. Pattnaik Jan 2012

A Single Amino Acid Change Resulting In Loss Of Fluorescence Of Egfp In A Viral Fusion Protein Confers Fitness And Growth Advantage To The Recombinant Vesicular Stomatitis Virus, Phat X. Dinh, Debasis Panda, Phani B. Das, Subash C. Das, Anshuman Das, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Using a recombinant vesicular stomatitis virus encoding eGFP fused in-frame with an essential viral replication protein, the phosphoprotein P, we show that during passage in culture, the virus mutates the nucleotide C289 within eGFP of the fusion protein PeGFP to A or T, resulting in R97S/C amino acid substitution and loss of fluorescence. The resultant non-fluorescent virus exhibits increased fitness and growth advantage over its fluorescent counterpart. The growth advantage of the non-fluorescent virus appears to be due to increased transcription and replication activities of the PeGFP protein carrying the R97S/C substitution. Further, our results show that the R97S/C mutation …


Fusion Of A Fluorescent Protein To The Pul25 Minor Capsid Protein Of Pseudorabies Virus Allows Live-Cell Capsid Imaging With Negligible Impact On Infection, Kevin P. Bohannon, Patricia J. Sollars, Gary E. Pickard, Gregory A. Smith Jan 2012

Fusion Of A Fluorescent Protein To The Pul25 Minor Capsid Protein Of Pseudorabies Virus Allows Live-Cell Capsid Imaging With Negligible Impact On Infection, Kevin P. Bohannon, Patricia J. Sollars, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

In order to resolve the location and activity of submicroscopic viruses in living cells, viral proteins are often fused to fluorescent proteins (FPs) and visualized by microscopy. In this study, we describe the fusion of FPs to three proteins of pseudorabies virus (PRV) that allowed imaging of capsids in living cells. Included in this study are the first recombinant PRV strains expressing FP–pUL25 fusions based on a design applied to herpes simplex virus type 1 by Homa and colleagues. The properties of each reporter virus were compared in both in vitro and in vivo infection models. PRV strains expressing FP–pUL25 …


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. Polan, Michael A. Barry, Karl A. Nath, Andrew D. Badley Jan 2012

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. Polan, 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 …


Dynamics Of Envelope Evolution In Clade C Shiv-Infected Pig-Tailed Macaques During Disease Progression Analyzed By Ultra-Deep Pyrosequencing, For Yue Tso, Damien C. Tully, Sandra Gonzalez, Christopher Quince, On Ho, Patricia Polacino, Ruth M. Ruprecht, Shiu-Lok Hu, Charles Wood Jan 2012

Dynamics Of Envelope Evolution In Clade C Shiv-Infected Pig-Tailed Macaques During Disease Progression Analyzed By Ultra-Deep Pyrosequencing, For Yue Tso, Damien C. Tully, Sandra Gonzalez, Christopher Quince, On Ho, Patricia Polacino, Ruth M. Ruprecht, Shiu-Lok Hu, Charles Wood

Nebraska Center for Virology: Faculty Publications

Understanding the evolution of the human immunodeficiency virus type 1 (HIV-1) envelope during disease progression can provide tremendous insights for vaccine development, and simian-human immunodeficiency virus (SHIV) infection of nonhuman primate provides an ideal platform for such studies. A newly developed clade C SHIV, SHIV-1157ipd3N4, which was able to infect rhesus macaques, closely resembled primary HIV-1 in transmission and pathogenesis, was used to infect several pig-tailed macaques. One of the infected animals subsequently progressed to AIDS, whereas one remained a nonprogressor. The viral envelope evolution in the infected animals during disease progression was analyzed by a bioinformatics approach using ultra-deep …


Molecular Genetic And Biochemical Characterization Of The Vaccinia Virus I3 Protein, The Replicative Single-Stranded Dna Binding Protein, Matthew D. Greseth, Kathleen A. Boyle, Matthew S. Bluma, Bethany Unger, Matthew S. Wiebe, Jamaria A. Soares-Martins, Nadi T. Wickramasekera, James Wahlberg, Paula Traktman Jan 2012

Molecular Genetic And Biochemical Characterization Of The Vaccinia Virus I3 Protein, The Replicative Single-Stranded Dna Binding Protein, Matthew D. Greseth, Kathleen A. Boyle, Matthew S. Bluma, Bethany Unger, Matthew S. Wiebe, Jamaria A. Soares-Martins, Nadi T. Wickramasekera, James Wahlberg, Paula Traktman

Nebraska Center for Virology: Faculty Publications

Vaccinia virus, the prototypic poxvirus, efficiently and faithfully replicates its approximately 200-kb DNA genome within the cytoplasm of infected cells. This intracellular localization dictates that vaccinia virus encodes most, if not all, of its own DNA replication machinery. Included in the repertoire of viral replication proteins is the I3 protein, which binds to single-stranded DNA (ssDNA) with great specificity and stability and has been presumed to be the replicative ssDNA binding protein (SSB). We substantiate here that I3 colocalizes with bromodeoxyuridine (BrdU)-labeled nascent viral genomes and that these genomes accumulate in cytoplasmic factories that are delimited by membranes derived from …


Lineage-Specific Differences Between Human And Simian Immunodeficiency Virus Regulation Of Gp120 Trimer Association And Cd4 Binding, Andrés Finzi, Beatriz Pacheco, Shi-Hua Xiang, Marie Pancera, Alon Herschhorn, Liping Wang, Xing Zeng, Anik Desormeaux, Peter D. Kwong, Joseph Sodroski Jan 2012

Lineage-Specific Differences Between Human And Simian Immunodeficiency Virus Regulation Of Gp120 Trimer Association And Cd4 Binding, Andrés Finzi, Beatriz Pacheco, Shi-Hua Xiang, Marie Pancera, Alon Herschhorn, Liping Wang, Xing Zeng, Anik Desormeaux, Peter D. Kwong, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

Metastable conformations of the gp120 and gp41 envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) must be maintained in the unliganded state of the envelope glycoprotein trimer. Binding of gp120 to the primary receptor, CD4, triggers the transition to an open conformation of the trimer, promoting interaction with the CCR5 chemokine receptor and ultimately leading to gp41-mediated virus-cell membrane fusion and entry. Topological layers in the gp120 inner domain contribute to gp120-trimer association in the unliganded state and to CD4 binding. Here we describe similarities and differences between HIV-1 and SIVmac gp120. In both …


Identification Of Molecular Determinants From Moloney Leukemia Virus 10 Homolog (Mov10) Protein For Virion Packaging And Anti-Hiv-1 Activity, Aierken Abudu, Xiaojun Wang, Ying Dang, Tao Zhou, Shi-Hua Xiang, Yong -Hui Zheng Jan 2012

Identification Of Molecular Determinants From Moloney Leukemia Virus 10 Homolog (Mov10) Protein For Virion Packaging And Anti-Hiv-1 Activity, Aierken Abudu, Xiaojun Wang, Ying Dang, Tao Zhou, Shi-Hua Xiang, Yong -Hui Zheng

Nebraska Center for Virology: Faculty Publications

Background: MOV10 inhibits HIV-1 replication after being packaged.

Results: A Gag binding plus all but one of seven helicase domains are required for MOV10 packaging. Nearly all residues are required for anti-HIV-1 activity. Conclusion: Gag binding is not sufficient for MOV10 packaging, and multiple discontinuous domains regulate MOV10 activity.

Significance: These findings uncover a new packaging mechanism and provide new insights into MOV10 antiviral activity.


Comparative Analysis Of The Fusion Efficiency Elicited By The Envelope Glycoprotein V1–V5 Regions Derived From Human Immunodeficiency Virus Type 1 Transmitted Perinatally, Hongyan Guo, Levon Abrahamyan, Chang Liu, Mackenzie Waltke, Yunqi Geng, Qimin Chen, Charles Wood, Xiaohong Kong Jan 2012

Comparative Analysis Of The Fusion Efficiency Elicited By The Envelope Glycoprotein V1–V5 Regions Derived From Human Immunodeficiency Virus Type 1 Transmitted Perinatally, Hongyan Guo, Levon Abrahamyan, Chang Liu, Mackenzie Waltke, Yunqi Geng, Qimin Chen, Charles Wood, Xiaohong Kong

Nebraska Center for Virology: Faculty Publications

Understanding the properties of viruses preferentially establishing infection during perinatal transmission of human immunodeficiency virus type 1 (HIV-1) is critical for the development of effective measures to prevent transmission. A previous study demonstrated that the newly transmitted viruses (in infants) of chronically infected mother–infant pairs (MIPs) were fitter in terms of growth, which was imparted by their envelope (Env) glycoprotein V1–V5 regions, than those in the corresponding chronically infected mothers. In order to investigate whether the higher fitness of transmitted viruses was conferred by their higher entry efficiency directed by the V1–V5 regions during perinatal transmission, the fusogenicity of Env …


Posttranslational Modification Of Vesicular Stomatitis Virus Glycoprotein, But Not Jnk Inhibition, Is The Antiviral Mechanism Of Sp600125, Sabrina Marozin, Jennifer Altomonte, Sibylle Apfel, Phat X. Dinh, Enrico De Toni, Antonia Rizzani, Andreas Nüssler, Nobuyuki Kato, Roland M. Schmid, Asit K. Pattnaik, Oliver Eberta Jan 2012

Posttranslational Modification Of Vesicular Stomatitis Virus Glycoprotein, But Not Jnk Inhibition, Is The Antiviral Mechanism Of Sp600125, Sabrina Marozin, Jennifer Altomonte, Sibylle Apfel, Phat X. Dinh, Enrico De Toni, Antonia Rizzani, Andreas Nüssler, Nobuyuki Kato, Roland M. Schmid, Asit K. Pattnaik, Oliver Eberta

School of Veterinary and Biomedical Sciences: Faculty Publications

Vesicular stomatitis virus (VSV), a negative-sense single-stranded-RNA rhabdovirus, is an extremely promising oncolytic agent for cancer treatment. Since oncolytic virotherapy is moving closer to clinical application, potentially synergistic combinations of oncolytic viruses and molecularly targeted antitumor agents are becoming a meaningful strategy for cancer treatment. Mitogenactivated protein kinase (MAPK) inhibitors have been shown to impair liver cell proliferation and tumor development, suggesting their potential use as therapeutic agents for hepatocellular carcinoma (HCC). In this work, we show that the impairment of MAPK in vitro did not interfere with the oncolytic properties of VSV in HCC cell lines. Moreover, the administration …


Glycosyl-Phosphatidylinositol (Gpi)-Anchored Membrane Association Of The Porcine Reproductive And Respiratory Syndrome Virus Gp4 Glycoprotein And Its Co-Localization With Cd163 In Lipid Rafts, Yijun Du, Asit K. Pattnaik, Cheng Song, Dongwan Yoo, Gang Li Jan 2012

Glycosyl-Phosphatidylinositol (Gpi)-Anchored Membrane Association Of The Porcine Reproductive And Respiratory Syndrome Virus Gp4 Glycoprotein And Its Co-Localization With Cd163 In Lipid Rafts, Yijun Du, Asit K. Pattnaik, Cheng Song, Dongwan Yoo, Gang Li

School of Veterinary and Biomedical Sciences: Faculty Publications

The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that …


Staphylococcal Response To Oxidative Stress, Rosmarie Gaupp, Nagender Ledala, Greg A. Somerville Jan 2012

Staphylococcal Response To Oxidative Stress, Rosmarie Gaupp, Nagender Ledala, Greg A. Somerville

School of Veterinary and Biomedical Sciences: Faculty Publications

Staphylococci are a versatile genus of bacteria that are capable of causing acute and chronic infections in diverse host species. The success of staphylococci as pathogens is due in part to their ability to mitigate endogenous and exogenous oxidative and nitrosative stress. Endogenous oxidative stress is a consequence of life in an aerobic environment; whereas, exogenous osidative and nitrosative stress are often due to the bacteria's interaction with host immune systems. To overcome the deleterious effects of oxidative and nitrosative stress, staphylococci have evolved protection, detoxification, and repair mechanisms that are controlled by a network of regulators. In this review, …


Effects Of Arterial Strain And Stress In The Prediction Of Restenosis Risk: Computer Modeling Of Stent Trials, Shijia Zhao, Linxia Gu, Stacey R. Froemming Jan 2012

Effects Of Arterial Strain And Stress In The Prediction Of Restenosis Risk: Computer Modeling Of Stent Trials, Shijia Zhao, Linxia Gu, Stacey R. Froemming

Department of Mechanical and Materials Engineering: Faculty Publications

Purpose — In-stenting restenosis is one of the major complications after stenting. Clinical trials of various stent designs have reported different restenosis rates. However, quantitative correlation between stent features and restenosis statistics is scant. In this work, it is hypothesized that stress concentrations on arterial wall caused artery injury, which initiates restenosis. The goal is to assess the correlation between stent-induced arterial stress and strain and the documented restenosis rates.

Methods — Six commercially available stents, including balloon-expandable stents and self-expanding stents, were virtually implanted into the arteries through finite element method. The resulted peak Von Mises stress, principal stress, …


Amino Acid Residues In The Non-Structural Protein 1 Of Porcine Reproductive And Respiratory Syndrome Virus Involved In Down-Regulation Of Tnf-Cx Expression In Vitro And Attenuation In Vivo, Sakthivel Subramaniam, Lalit Beura, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio Jan 2012

Amino Acid Residues In The Non-Structural Protein 1 Of Porcine Reproductive And Respiratory Syndrome Virus Involved In Down-Regulation Of Tnf-Cx Expression In Vitro And Attenuation In Vivo, Sakthivel Subramaniam, Lalit Beura, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses tumor necrosis factor-alpha (TNF-α) production at both transcriptional and post-transcriptional levels by its non-structural proteins 1α and 1β (Nsp1α and Nsp1β). To identifY the amino acid residues responsible for this activity, we generated several alanine substitution mutants of Nsp1α and Nsp1β. Examination of the mutant proteins revealed that Nsp1α residues Gly90, Asn91 , Arg97, Argl 00 and Arg124 were necessary for TNF-α promoter suppression, whereas several amino acids spanning the entire Nsp1β ~ were found to be required for this activity. Two mutant viruses, with mutations at Nsp1α Gly90 or Nsp1β residues …


Antibody Responses To Lytic And Latent Human Herpesvirus 8 Antigens Among Hiv-Infected Patients In Central China, Tiejun Zhang, Na He, Yingying Ding, Qingwu Jiang, Charles Wood Jan 2012

Antibody Responses To Lytic And Latent Human Herpesvirus 8 Antigens Among Hiv-Infected Patients In Central China, Tiejun Zhang, Na He, Yingying Ding, Qingwu Jiang, Charles Wood

Nebraska Center for Virology: Faculty Publications

Human herpesvirus 8 (HHV8) is an important opportunistic infection of HIV/AIDS. However, very little is known about antibody seropositivities to HHV8 lytic and latent antigens among HIVinfected patients in China. Therefore, a cross-sectional study was conducted to explore HHV8 serostatus among 316 HIV-infected patients in a rural area of central China. The antibody seropositivity to HHV8 ORF65 (lytic) and LANA (latent) antigens was 12.7% and 10.4%, respectively. Patients who were naïve to antiretroviral therapy (ART) were more likely to be seropositive for antibodies to ORF65 (OR: 3.79; 95% CI: 1.71–8.42) and LANA (OR: 3.77; 95% CI: 1.55–9.14) than patients receiving …


Triticum Mosaic Poacevirus Enlists P1 Rather Than Hc-Pro To Suppress Rna Silencing-Mediated Host Defense, Satyanarayana Tatineni, Feng Qu, Ruhui Li, Thomas Jack Morris, Roy French Jan 2012

Triticum Mosaic Poacevirus Enlists P1 Rather Than Hc-Pro To Suppress Rna Silencing-Mediated Host Defense, Satyanarayana Tatineni, Feng Qu, Ruhui Li, Thomas Jack Morris, Roy French

Nebraska Center for Virology: Faculty Publications

Triticum mosaic virus (TriMV) is the type species of the newly established Poacevirus genus in the family Potyviridae. In this study, we demonstrate that in contrast to the helper component- proteinase (HC-Pro) of Potyvirus species, the P1 proteins of TriMV and Sugarcane steak mosaic poacevirus function in suppression of RNA silencing (SRS). TriMV P1 effectively suppressed silencing induced by single- or double-stranded RNAs (ss/ds RNAs), and disrupted the systemic spread of silencing signals at a step after silencing signal production. Interestingly, contrary to enhanced SRS activity of potyviral HC-Pro by co-expression with P1, the presence of TriMV HC-Pro reduced …