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Full-Text Articles in Biological Phenomena, Cell Phenomena, and Immunity

The Vaccinia Virus (Vacv) B1 And Cellular Vrk2 Kinases Promote Vacv Replication Factory Formation Through Phosphorylation-Dependent Inhibition Of Vacv B12, Annabel T. Olson, Zhigang Wang, Annabel Olson, Alexandria C. Linville, Brianna L. Bullard, Eric A. Weaver, Clinton Jones, Matthew S. Wiebe Jan 2019

The Vaccinia Virus (Vacv) B1 And Cellular Vrk2 Kinases Promote Vacv Replication Factory Formation Through Phosphorylation-Dependent Inhibition Of Vacv B12, Annabel T. Olson, Zhigang Wang, Annabel Olson, Alexandria C. Linville, Brianna L. Bullard, Eric A. Weaver, Clinton Jones, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and vi- ral origin. The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). Recent evidence indicates that B1 and VRK2 mediate a com- mon pathway that is largely uncharacterized but appears independent of previous VRK substrates. Interestingly, separate studies described a novel role for B1 in inhibiting vac- cinia virus protein B12, which otherwise impedes an early event in the …


Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges To Clinical Application, Henry Caplan, Scott D Olson, Akshita Kumar, Mitchell George, Karthik S Prabhakara, Pamela Wenzel, Supinder Bedi, Naama E Toledano-Furman, Fabio Triolo, Julian Kamhieh-Milz, Guido Moll, Charles S Cox Jan 2019

Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges To Clinical Application, Henry Caplan, Scott D Olson, Akshita Kumar, Mitchell George, Karthik S Prabhakara, Pamela Wenzel, Supinder Bedi, Naama E Toledano-Furman, Fabio Triolo, Julian Kamhieh-Milz, Guido Moll, Charles S Cox

Faculty, Staff and Student Publications

For several decades, multipotent mesenchymal stromal cells (MSCs) have been extensively studied for their therapeutic potential across a wide range of diseases. In the preclinical setting, MSCs demonstrate consistent ability to promote tissue healing, down-regulate excessive inflammation and improve outcomes in animal models. Several proposed mechanisms of action have been posited and demonstrated across an array of in vitro models. However, translation into clinical practice has proven considerably more difficult. A number of prominent well-funded late-phase clinical trials have failed, thus calling out for new efforts to optimize product delivery in the clinical setting. In this review, we discuss novel …


An Ensemble Of Flexible Conformations Underlies Mechanotransduction By The Cadherin–Catenin Adhesion Complex, Martin Bush, Bashir M. Alhanshali, Shuo Qian, Christopher B. Stanley, William T. Heller, Tsutomu Matsui, Thomas M. Weiss, Iain D. Nicholl, Thomas Walz, David J. E. Callaway, Zimei Bu Jan 2019

An Ensemble Of Flexible Conformations Underlies Mechanotransduction By The Cadherin–Catenin Adhesion Complex, Martin Bush, Bashir M. Alhanshali, Shuo Qian, Christopher B. Stanley, William T. Heller, Tsutomu Matsui, Thomas M. Weiss, Iain D. Nicholl, Thomas Walz, David J. E. Callaway, Zimei Bu

Publications and Research

The cadherin–catenin adhesion complex is the central component of the cell–cell adhesion adherens junctions that transmit mechanical stress from cell to cell. We have determined the nanoscale structure of the adherens junction complex formed by the α-catenin•β-catenin•epithelial cadherin cytoplasmic domain (ABE) using negative stain electron microscopy, small-angle X-ray scattering, and selective deuteration/small-angle neutron scattering. The ABE complex is highly pliable and displays a wide spectrum of flexible structures that are facilitated by protein-domain motions in α- and β-catenin. Moreover, the 107-residue intrinsically disordered N-terminal segment of β-catenin forms a flexible “tongue” that is inserted into α-catenin and participates in the …


Efficacy Of A T Cell-Biased Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, Matthew J. Gorman, Michael S. Diamond, Eric A. Weaver Dec 2018

Efficacy Of A T Cell-Biased Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, Matthew J. Gorman, Michael S. Diamond, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV) is a major public health concern due to the risk of congenital Zika syndrome in developing fetuses and Guillain-Barre syndrome in adults. Currently, there are no approved vaccines available to protect against infection. Adenoviruses are safe and highly immunogenic vaccine vectors capable of inducing lasting humoral and cellular immune responses. Here, we developed two Adenovirus (Ad) vectored Zika virus vaccines by inserting a ZIKV prM-E gene expression cassette into human Ad types 4 (Ad4-prM-E) and 5 (Ad5-prM-E). Immune correlates indicate that Ad5-prM-E vaccination induces both an anti-ZIKV antibody and T-cell responses whereas Ad4-prM-E vaccination only induces a …


Potential Role Of Csf Cytokine Profiles In Discriminating Infectious From Non-Infectious Cns Disorders., Danielle Fortuna, D. Craig Hooper, Amity L. Roberts, Larry A. Harshyne, Michelle Nagurney, Mark T. Curtis Oct 2018

Potential Role Of Csf Cytokine Profiles In Discriminating Infectious From Non-Infectious Cns Disorders., Danielle Fortuna, D. Craig Hooper, Amity L. Roberts, Larry A. Harshyne, Michelle Nagurney, Mark T. Curtis

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Current laboratory testing of cerebrospinal fluid (CSF) does not consistently discriminate between different central nervous system (CNS) disease states. Rapidly distinguishing CNS infections from other brain and spinal cord disorders that share a similar clinical presentation is critical. New approaches focusing on aspects of disease biology, such as immune response profiles that can have stimulus-specific attributes, may be helpful. We undertook this preliminary proof-of-concept study using multiplex ELISA to measure CSF cytokine levels in various CNS disorders (infections, autoimmune/demyelinating diseases, lymphomas, and gliomas) to determine the potential utility of cytokine patterns in differentiating CNS infections from other CNS diseases. Both …


Neutrophil To Lymphocyte Ratio: A Prognostic Indicator For Astronaut Health, Amber M. Paul, Siddhita D. Mhatre, Egle Cekanaviciute, Ann-Sofie Schreurs, Candice G.T. Tahimic, Ruth K. Globus, Brian Crucian, Sharmila Bhattacharya Oct 2018

Neutrophil To Lymphocyte Ratio: A Prognostic Indicator For Astronaut Health, Amber M. Paul, Siddhita D. Mhatre, Egle Cekanaviciute, Ann-Sofie Schreurs, Candice G.T. Tahimic, Ruth K. Globus, Brian Crucian, Sharmila Bhattacharya

Publications

Short-term and long-term spaceflight missions can cause immune system dysfunction in astronauts. Recent studies indicate elevated white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in astronaut blood, along with unchanged or reduced lymphocyte counts, and reduced T cell function, during short-(days) and long-(months) term spaceflight. A high PMN to lymphocyte ratio (NLR) can acts as a strong predictor of poor prognosis in cancer, and as a biomarker for subclinical inflammation in humans and chronic stress in mouse models, however, the NLR has not yet been identified as a predictor of astronaut health during spaceflight. For this, complete blood cell count …


Kaposi’S Sarcoma-Associated Herpesvirus Seropositivity Is Associated With Type 2 Diabetes Mellitus: A Case–Control Study In Xinjiang, China, Meng Cui, Qiwen Fang, Jun Zheng, Zhanjun Shu, Yin Chen, Yage Fan, Juan Zhao, Charles Wood, Tiejun Zhang, Yan Zeng Oct 2018

Kaposi’S Sarcoma-Associated Herpesvirus Seropositivity Is Associated With Type 2 Diabetes Mellitus: A Case–Control Study In Xinjiang, China, Meng Cui, Qiwen Fang, Jun Zheng, Zhanjun Shu, Yin Chen, Yage Fan, Juan Zhao, Charles Wood, Tiejun Zhang, Yan Zeng

Nebraska Center for Virology: Faculty Publications

Objective: To assess the potential relationship between Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and type 2 diabetes mellitus (DM-2) in Xinjiang, China.

Methods: A case–control study of consecutively included DM-2 patients and normal controls was conducted among the Uygur and Han populations in Xinjiang Uygur Autonomous Region, China. Blood samples were collected and KSHV seroprevalence, antibody titers, and viral load were investigated. Logistic regression analysis and multiple linear regression analysis were applied to explore determinants of the main outcome measures.

Results: A total of 324 patients with DM-2 and 376 normal controls were included. The seroprevalence of KSHV was 49.1% (95% …


Gene Gangs Of The Chloroviruses: Conserved Clusters Of Collinear Monocistronic Genes, Phillip Seitzer, Adrien Jeanniard, Fangrui Ma, James L. Van Etten, Marc T. Facciotti, David D. Dunigan Oct 2018

Gene Gangs Of The Chloroviruses: Conserved Clusters Of Collinear Monocistronic Genes, Phillip Seitzer, Adrien Jeanniard, Fangrui Ma, James L. Van Etten, Marc T. Facciotti, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses (family Phycodnaviridae) are dsDNA viruses found throughout the world’s inland waters. The open reading frames in the genomes of 41 sequenced chloroviruses (330 + 40 kbp each) representing three virus types were analyzed for evidence of evolutionarily conserved local genomic “contexts”, the organization of biological information into units of a scale larger than a gene. Despite a general loss of synteny between virus types, we informatically detected a highly conserved genomic context defined by groups of three or more genes that we have termed “gene gangs”. Unlike previously described local genomic contexts, the definition of gene gangs requires only …


Experimental Evaluation Of The Importance Of Colonization History In Early-Life Gut Microbiota Assembly, Inés Martínez, Maria X. Maldonado-Gomez, João Carlos Gomes-Neto, Hatem Kittana, Hua Ding, Robert J. Schmaltz, Payal Joglekar, Roberto Jiménez Cardona, Nathan L Marsteller, Steven W. Kembel, Andrew K. Benson, Daniel A. Peterson, Amanda Ramer-Tait, Jens C. Walter Sep 2018

Experimental Evaluation Of The Importance Of Colonization History In Early-Life Gut Microbiota Assembly, Inés Martínez, Maria X. Maldonado-Gomez, João Carlos Gomes-Neto, Hatem Kittana, Hua Ding, Robert J. Schmaltz, Payal Joglekar, Roberto Jiménez Cardona, Nathan L Marsteller, Steven W. Kembel, Andrew K. Benson, Daniel A. Peterson, Amanda Ramer-Tait, Jens C. Walter

Department of Food Science and Technology: Faculty Publications

The factors that govern assembly of the gut microbiota are insufficiently understood. Here, we test the hypothesis that inter-individual microbiota variation can arise solely from differences in the order and timing by which the gut is colonized early in life. Experiments in which mice were inoculated in sequence either with two complex seed communities or a cocktail of four bacterial strains and a seed community revealed that colonization order influenced both the outcome of community assembly and the ecological success of individual colonizers. Historical contingency and priority effects also occurred in Rag1-/- mice, suggesting that the adaptive immune system …


Susceptibility Genes To Plant Viruses, Hernan Garcia-Ruiz Sep 2018

Susceptibility Genes To Plant Viruses, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Plant viruses use cellular factors and resources to replicate and move. Plants respond to viral infection by several mechanisms, including innate immunity, autophagy, and gene silencing, that viruses must evade or suppress. Thus, the establishment of infection is genetically determined by the availability of host factors necessary for virus replication and movement and by the balance between plant defense and viral suppression of defense responses. Host factors may have antiviral or proviral activities. Proviral factors condition susceptibility to viruses by participating in processes essential to the virus. Here, we review current advances in the identification and characterization of host factors …


Evaluation Of Endothelial Cell Responses To Elevated Glucose, Gabriella Sugerman Aug 2018

Evaluation Of Endothelial Cell Responses To Elevated Glucose, Gabriella Sugerman

Master's Theses

Developing a tissue-engineered Blood Vessel Mimic (BVM) to represent diabetic macrovascular disease could expedite design of new vascular devices specifically tailored to diabetic patients. In contribution toward this model, this thesis assessed Human Umbilical Vein Endothelial Cell (HUVEC) responses to high glucose conditions. Interleukin 6 (IL-6) and Cluster of Differentiation 36 (CD36) were selected to signify oxidative stress activity, a hallmark of diabetic macrovascular disease. Next, activity of potential reference genes B2M, HPRT1, and ACTB was assessed. All genes were found to exceed acceptable variability, so the E-ΔC T method of data analysis was selected. Next, cellular responses to high …


Defining The Radioresponse Of Mossy Cells, Devon Ivy Jun 2018

Defining The Radioresponse Of Mossy Cells, Devon Ivy

Electronic Theses, Projects, and Dissertations

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in …


Alcohol Drives Oxidation-Dependent Desensitization Of Airway Cilia Motility Responsiveness, Michael Price May 2018

Alcohol Drives Oxidation-Dependent Desensitization Of Airway Cilia Motility Responsiveness, Michael Price

Theses & Dissertations

Alcohol abuse, which can impair clearance of pathogens and debris from the airway, is associated with an increase in complications and a higher mortality rate during the progression of pneumonia. With prolonged alcohol exposure, mucociliary clearance (MCC), which depends on the coordinated beating of cilia, is dysfunctional. Effective MCC relies on cAMP-dependent protein kinase (PKA) activation of ciliary beat frequency (CBF). PKA activation and stimulation of CBF are blunted with chronic exposure to alcohol. This phenomenon is known as alcohol-induced ciliary dysfunction (AICD). Previous studies have shown that concomitant feeding of mice with alcohol and antioxidants prevents AICD, suggesting a …


Ferrocenylchalcone-Uracil Conjugates: Synthesis And Cytotoxic Evaluation, Amandeep Singh, Vishu Mehra, Neda Sadeghiani, Saghar Mozaffari, Keykavous Parang, Vipan Kumar Feb 2018

Ferrocenylchalcone-Uracil Conjugates: Synthesis And Cytotoxic Evaluation, Amandeep Singh, Vishu Mehra, Neda Sadeghiani, Saghar Mozaffari, Keykavous Parang, Vipan Kumar

Pharmacy Faculty Articles and Research

Huisgen’s azide-alkyne cycloaddition reaction was employed to synthesize a series of 1H-1,2,3-triazole-tethered uracil-ferrocenyl chalcone conjugates with the aim of evaluating their in vitro anti-proliferative efficacy on human leukemia (CCRF-CEM) and human breast adenocarcinoma (MDA-MB-468) cell lines. Cytotoxic evaluation studies identified a number of synthesized conjugates that inhibited the proliferation of leukemia cancer cells by ~70% after 72 h. The selected synthesized conjugates were found to be significantly less cytotoxic against normal kidney cell line (LLC-PK1) when compared with CCRF-CEM cancer cells.


Exploring The Regulatory Mechanism Of The Notch Ligand Receptor Jagged1 Via The Aryl Hydrocarbon Receptor In Breast Cancer, Sean Alan Piwarski Jan 2018

Exploring The Regulatory Mechanism Of The Notch Ligand Receptor Jagged1 Via The Aryl Hydrocarbon Receptor In Breast Cancer, Sean Alan Piwarski

Theses, Dissertations and Capstones

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that binds pollutants, therapeutic drugs and endogenous ligands. AHR is of particular interest in cancer and has been shown to play roles in both tumor progression and tumor suppression. As a result, it has received growing attention as a possible chemotherapeutic target. AHR is expressed in all breast cancer subtypes and can promote or inhibit breast cancer depending on the ligand it binds. The Notch signaling pathway is a highly conserved evolutionary pathway that plays extremely vital roles during development by regulating cell fate and differentiation. Notch signaling has increasingly …


Altered Ratio Of T Follicular Helper Cells To T Follicular Regulatory Cells Correlates With Autoreactive Antibody Response In Simian Immunodeficiency Virus–Infected Rhesus Macaques, Wenjin Fan, Andrew James Demers, Yanmin Wan, Qingsheng Li Jan 2018

Altered Ratio Of T Follicular Helper Cells To T Follicular Regulatory Cells Correlates With Autoreactive Antibody Response In Simian Immunodeficiency Virus–Infected Rhesus Macaques, Wenjin Fan, Andrew James Demers, Yanmin Wan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Individuals with chronic HIV-1 infection have an increased prevalence of autoreactive Abs. Many of the isolated HIV broadly neutralizing Abs from these individuals are also autoreactive. However, the underlying mechanism(s) that produce these autoreactive broadly neutralizing Abs remains largely unknown. The highly regulated coordination among B cells, T follicular helper (TFH) cells, and T follicular regulatory (TFR) cells in germinal centers (GCs) of peripheral lymphatic tissues (LTs) is essential for defense against pathogens while also restricting autoreactive responses. We hypothesized that an altered ratio of TFH/TFR cells in the GC contributes to the …


Mucosal Antibody Responses To Vaccines Targeting Siv Protease Cleavage Sites Or Fulllength Gag And Env Proteins In Mauritian Cynomolgus Macaques, Hongzhao Li, Yan Hai, So-Yon Lim, Nikki Toledo, Jose Crecente-Campo, Dane Schalk, Lin Li, Robert W. Omange, Tamara G. Dacoba, Lewis R. Liu, Mohammad Abul Kashem, Yanmin Wan, Binhua Liang, Qingsheng Li, Eva Rakasz, Nancy Schultz-Darken, Maria J. Alonso, Francis A. Plummer, James B. Whitney, Ma Luo Jan 2018

Mucosal Antibody Responses To Vaccines Targeting Siv Protease Cleavage Sites Or Fulllength Gag And Env Proteins In Mauritian Cynomolgus Macaques, Hongzhao Li, Yan Hai, So-Yon Lim, Nikki Toledo, Jose Crecente-Campo, Dane Schalk, Lin Li, Robert W. Omange, Tamara G. Dacoba, Lewis R. Liu, Mohammad Abul Kashem, Yanmin Wan, Binhua Liang, Qingsheng Li, Eva Rakasz, Nancy Schultz-Darken, Maria J. Alonso, Francis A. Plummer, James B. Whitney, Ma Luo

Nebraska Center for Virology: Faculty Publications

HIV mutates rapidly and infects CD4+ T cells, especially when they are activated. A vaccine targeting conserved, essential viral elements while limiting CD4+ T cell activation could be effective. Learning from natural immunity observed in a group of highly HIV-1 exposed seronegative Kenyan female sex workers, we are testing a novel candidate HIV vaccine targeting the 12 viral protease cleavage sites (PCSs) (the PCS vaccine), in comparison with a vaccine targeting full-length Gag and Env (the Gag/Env vaccine) in a Mauritian cynomolgus macaque/SIV model. In this study we evaluated these vaccines for induction of mucosal antibodies to SIV …


Sivcpz Closely Related To The Ancestral Hiv-1 Is Less Or Non-Pathogenic To Humans In A Hu-Blt Mouse Model, Zhe Yuan, Guobin Kang, Lance Daharsh, Wenjin Fan, Qingsheng Li Jan 2018

Sivcpz Closely Related To The Ancestral Hiv-1 Is Less Or Non-Pathogenic To Humans In A Hu-Blt Mouse Model, Zhe Yuan, Guobin Kang, Lance Daharsh, Wenjin Fan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

The HIV-1 pandemic is a consequence of the cross-species transmission of simian immunodeficiency virus in wild chimpanzees (SIVcpz) to humans. Our previous study demonstrated SIVcpz strains that are closely related to the ancestral viruses of HIV-1 groups M (SIVcpzMB897) and N (SIVcpzEK505) and two SIVcpz lineages that are not associated with any known HIV-1 infections in humans (SIVcpzMT145 and SIVcpzBF1167), all can readily infect and robustly replicate in the humanized-BLT mouse model of humans. However, the comparative pathogenicity of different SIVcpz strains remains unknown. Herein, we compared the pathogenicity of the above four SIVcpz strains with HIV-1 using humanized-BLT mice. …


Identification Of Unequally Represented Founder Viruses Among Tissues In Very Early Siv Rectal Transmission, Jian Chen, Yanqin Ren, Lance Daharsh, Lu Liu, Guobin Kang, Qingsheng Li, Qiang Wei, Yanmin Wu, Jianqing Xu Jan 2018

Identification Of Unequally Represented Founder Viruses Among Tissues In Very Early Siv Rectal Transmission, Jian Chen, Yanqin Ren, Lance Daharsh, Lu Liu, Guobin Kang, Qingsheng Li, Qiang Wei, Yanmin Wu, Jianqing Xu

Nebraska Center for Virology: Faculty Publications

Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission.We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 104 TCID50) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses …


Analytical Performance Of A Low‐Cost Multiplex Polymerase Chain Reaction Human Papillomavirus Genotyping Assay For Use In Sub‐Saharan Africa, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Daniela Gonzalez, John T. West, Charles Wood, Joel Palefsky, Peter C. Angeletti Jan 2018

Analytical Performance Of A Low‐Cost Multiplex Polymerase Chain Reaction Human Papillomavirus Genotyping Assay For Use In Sub‐Saharan Africa, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Daniela Gonzalez, John T. West, Charles Wood, Joel Palefsky, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

We have tested a multiplex polymerase chain reaction (PCR) human papillomavirus (HPV) genotyping assay to fill the need for rapid and low‐cost HPV detection in Sub‐ Saharan Africa. This method allows high throughput genotyping and simultaneous detection of 14 high‐risk and two low‐risk HPV types, by PCR amplification of HPV DNAs in a single reaction tube. In this study, we describe stepwise experiments to validate the multiplex HPV PCR assay for determination of HPV genotypes from 104 cervical brush samples from Tanzanian women. Assay performance was evaluated by determination of intra‐laboratory reproducibility, sensitivity, and specificity. Further performance was assessed by …


Discovery Of A Non-Nucleoside Rna Polymerase Inhibitor For Blocking Zika Virus Replication Through In Silico Screening, Aryamav Pattnaik, Nicholas Palermo, Bikash R. Sahoo, Zhe Yuan, Duoyi Hu, Arun S. Annamalai, Hiep L. X. Vu, Ignacio Correas, Pavan Kumar Prathipati, Christopher J. Destache, Qingsheng Li, Fernando A. Osorio, Asit K. Pattnaik, Shi-Hua Xiang Jan 2018

Discovery Of A Non-Nucleoside Rna Polymerase Inhibitor For Blocking Zika Virus Replication Through In Silico Screening, Aryamav Pattnaik, Nicholas Palermo, Bikash R. Sahoo, Zhe Yuan, Duoyi Hu, Arun S. Annamalai, Hiep L. X. Vu, Ignacio Correas, Pavan Kumar Prathipati, Christopher J. Destache, Qingsheng Li, Fernando A. Osorio, Asit K. Pattnaik, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV), an emerging arbovirus, has become a major human health concern globally due to its association with congenital abnormalities and neurological diseases. Licensed vaccines or antivirals against ZIKV are currently unavailable. Here, by employing a structure-based approach targeting the ZIKV RNA-dependent RNA polymerase (RdRp), we conducted in silico screening of a library of 100,000 small molecules and tested the top ten lead compounds for their ability to inhibit the virus replication in cell-based in vitro assays. One compound, 3-chloro-N-[({4-[4-(2-thienylcarbonyl)-1-piperazinyl]phenyl}amino)carbonothioyl]-1-benzothiophene-2-carboxamide (TPB), potently inhibited ZIKV replication at submicromolar concentrations. Molecular docking analysis suggests that …


Non-Naturally Occurring Porcine Reproductive And Respiratory Syndrome Virus (Prrsv) And Methods Of Using, Hiep Lai Xuan Vu, Fernando Osorio, William W. Laegreid, Asit K. Pattnaik, Fangrui Ma Jan 2018

Non-Naturally Occurring Porcine Reproductive And Respiratory Syndrome Virus (Prrsv) And Methods Of Using, Hiep Lai Xuan Vu, Fernando Osorio, William W. Laegreid, Asit K. Pattnaik, Fangrui Ma

Nebraska Center for Virology: Faculty Publications

A non-naturally occurring porcine reproductive and respiratory syndrome virus (PRRSV) is provided herein, and methods of making and using the non-naturally occurring PRRSV also are provided.


Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Eun Hee Kwon, Peter Julius, Qingsheng Li, John T. West, Charles Wood Jan 2018

Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Eun Hee Kwon, Peter Julius, Qingsheng Li, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Subtype C HIV-1 is responsible for the largest proportion of people living with HIV-1 infection. However, there is limited information about the roles of the brain and its cell types as a potential sanctuary for this subtype and how the sanctuary may be affected by the administration of anti-retroviral therapy (ART). To address this issue, we collected postmortem brain tissues from ART treated HIV-1 infected Zambian individuals who experienced complete viral suppression and those who did not. Tissues from various brain compartments were collected from each individual as frozen and formalin-fixed paraffin embedded brain specimens, for detection and quantification of …


Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Peter Julius, Qingsheng Li, John T. West, Charles Wood Jan 2018

Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Peter Julius, Qingsheng Li, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Subtype C HIV-1 is responsible for the largest proportion of people living with HIV-1 infection. However, there is limited information about the roles of the brain and its cell types as a potential sanctuary for this subtype and how the sanctuary may be affected by the administration of anti-retroviral therapy (ART). To address this issue, we collected postmortem brain tissues from ART treated HIV-1 infected Zambian individuals who experienced complete viral suppression and those who did not. Tissues from various brain compartments were collected from each individual as frozen and formalin-fixed paraffin embedded brain specimens, for detection and quantification of …


Contribution Of The Gp120 V3 Loop To Envelope Glycoprotein Trimer Stability In Primate Immunodeficiency Viruses, Dane Bowder, Haley Hollingsead, Kate Durst, Duoyi Hu, Wenzhong Wei, Joshua Wiggins, Halima Medjahed, Andrés Finzi, Joseph Sodroski, Shi-Hua Xiang Jan 2018

Contribution Of The Gp120 V3 Loop To Envelope Glycoprotein Trimer Stability In Primate Immunodeficiency Viruses, Dane Bowder, Haley Hollingsead, Kate Durst, Duoyi Hu, Wenzhong Wei, Joshua Wiggins, Halima Medjahed, Andrés Finzi, Joseph Sodroski, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The V3 loop of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein (Env) becomes exposed after CD4 binding and contacts the coreceptor to mediate viral entry. Prior to CD4 engagement, a hydrophobic patch located at the tip of the V3 loop stabilizes the non-covalent association of gp120 with the Env trimer of HIV-1 subtype B strains. Here, we show that this conserved hydrophobic patch (amino acid residues 307, 309 and 317) contributes to gp120-trimer association in HIV-1 subtype C, HIV-2 and SIV. Changes that reduced the hydrophobicity of these V3 residues resulted in increased gp120 shedding and …


Ultrastructure Of Meelsvirus: A Nuclear Virus Of Arrow Worms (Phylum Chaetognatha) Producing Giant "Tailed" Virions, George L. Shinn, Brianna L. Bullard Jan 2018

Ultrastructure Of Meelsvirus: A Nuclear Virus Of Arrow Worms (Phylum Chaetognatha) Producing Giant "Tailed" Virions, George L. Shinn, Brianna L. Bullard

Nebraska Center for Virology: Faculty Publications

Most known giant viruses, i.e., viruses producing giant virions, parasitize amoebae and other unicellular eukaryotes. Although they vary in the level of dependence on host nuclear functions, their virions self-assemble in the host cell's cytoplasm. Here we report the discovery of a new prototype of giant virus infecting epidermal cells of the marine arrow worm Adhesisagitta hispida. Its 1.25 μm-long virions self-assemble and accumulate in the host cell's nucleus. Conventional transmission electron microscopy reveals that the virions have a unique bipartite structure. An ovoid nucleocapsid, situated in a broad "head" end of the virion is surrounded by a thin …


Membrane Bound Il21 Promotes Natural Killer Cell Expansion Through Mir 124-3p Mediated Regulation, Anitha Somanchi Dec 2017

Membrane Bound Il21 Promotes Natural Killer Cell Expansion Through Mir 124-3p Mediated Regulation, Anitha Somanchi

Dissertations and Theses (Open Access)

Natural Killer (NK) cells are cells of the innate immune system that act as first line of defense against viral infections and participate in tumor immune surveillance. NK cells do not cause graft versus host disease (GvHD), or require prior antigen exposure to exert anti-tumor activity, hence are an attractive choice for immunotherapy applications. Owing to small numbers of NK cells in peripheral blood (1-32%, with a 6% median), ex vivo expansion of NK cells is critical for NK cell adoptive immunotherapy, various expansion platforms have been explored over the decades. We developed a robust platform for ex vivo expansion …


Development Of A Broadly Protective Modified-Live Virus Vaccine Candidate Against Porcine Reproductive And Respiratory Syndrome Virus, Haiyan Sun, Aspen Workman, Fernando A. Osorio, David J. Steffen, Hiep L.X. Vu Nov 2017

Development Of A Broadly Protective Modified-Live Virus Vaccine Candidate Against Porcine Reproductive And Respiratory Syndrome Virus, Haiyan Sun, Aspen Workman, Fernando A. Osorio, David J. Steffen, Hiep L.X. Vu

Nebraska Center for Virology: Faculty Publications

Modified-live virus (MLV) vaccines are widely used to protect pigs against porcine reproductive and respiratory syndrome virus (PRRSV). However, current MLV vaccines do not confer adequate levels of heterologous protection, presumably due to the substantial genetic diversity of PRRSV isolates circulating in the field. To overcome this genetic variation challenge, we recently generated a synthetic PRRSV strain containing a consensus genomic sequence of PRRSV-2. We demonstrated that our synthetic PRRSV strain confers unprecedented levels of heterologous protection. However, the synthetic PRRSV strain at passage 1 (hereafter designated CON-P1) is highly virulent and therefore, is not suitable to be used as …


Efficacy Of An Adenoviral Vectored Multivalent Centralized Influenza Vaccine, Amy Lingel, Brianna L. Bullard, Eric A. Weaver Nov 2017

Efficacy Of An Adenoviral Vectored Multivalent Centralized Influenza Vaccine, Amy Lingel, Brianna L. Bullard, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Mice were immunized with Adenovirus expressing the H1-con, H2-con, H3-con and H5-con HA consensus genes in combination (multivalent) and compared to mice immunized with the traditional 2010–2011 FluZone and FluMist seasonal vaccines. Immunized mice were challenged with 10–100 MLD50 of H1N1, H3N1, H3N2 and H5N1 influenza viruses. The traditional vaccines induced robust levels of HA inhibition (HI) titers, but failed to protect against five different heterologous lethal influenza challenges. Conversely, the multivalent consensus vaccine (1 × 1010 virus particles (vp)/mouse) induced protective HI titers of ≥40 against 8 of 10 influenza viruses that represent a wide degree of divergence within …


Prevalence Of Kaposi’S Sarcoma-Associated Herpesvirus In Uygur And Han Populations From The Urumqi And Kashgar Regions Of Xinjiang, China, Jun Zheng, Yang Yang, Meng Cui, Zhan-Jun Shu, Li-Li Han, Zhen-Qiu Liu, Charles Wood, Tiejun Zhang, Yan Zeng Sep 2017

Prevalence Of Kaposi’S Sarcoma-Associated Herpesvirus In Uygur And Han Populations From The Urumqi And Kashgar Regions Of Xinjiang, China, Jun Zheng, Yang Yang, Meng Cui, Zhan-Jun Shu, Li-Li Han, Zhen-Qiu Liu, Charles Wood, Tiejun Zhang, Yan Zeng

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the infectious etiologic agent associated with Kaposi’s sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease. It has been shown that high KSHV prevalence and high incidence of both classic KS and AIDSassociated KS are found mostly among people of Uygur ethnicity in Xinjiang, while people of Han ethnicity in Xinjiang have a higher KSHV seroprevalence than those of other Han populations in mainland China. However, it is still unclear why there is such geographical and population variation in KSHV distribution in China. In this work, we focused on the populations in the Kashgar region …