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Viral And Immunological Analytes Are Poor Predictors Of The Clinical Treatment Response In Kaposi’S Sarcoma Patients, Salum J. Lidenge, For Yue Tso, Yasaman Mortazavi, John R. Ngowi, Danielle M. Shea, Julius Mwaiselage, Charles Wood, John T. West 2020 Nebraska Center for Virology & University of Nebraska-Lincoln & Ocean Road Cancer Institute & Muhimbili University of Health and Allied Sciences

Viral And Immunological Analytes Are Poor Predictors Of The Clinical Treatment Response In Kaposi’S Sarcoma Patients, Salum J. Lidenge, For Yue Tso, Yasaman Mortazavi, John R. Ngowi, Danielle M. Shea, Julius Mwaiselage, Charles Wood, John T. West

Virology Papers

Kaposi’s sarcoma-associated herpes virus (KSHV) is the etiologic agent for Kaposi’s sarcoma (KS). The prognostic utility of KSHV and HIV-1 (human immunodeficiency virus) viremia as well as immunological parameters in clinical management of participants with KS is unclear. The objective of this study was to investigate viral and immunological parameters as predictors of KS treatment responses in participants with KS from sub-Saharan Africa (SSA). Plasma KSHV-DNA, HIV-1 viral load, total anti-KSHV antibody, KSHV-neutralizing antibody (nAb), cytokine/chemokine levels, and T-cell differentiation subsets were quantified before and after KS treatment in 13 participants with KS and in 13 KSHV-infected ...


Hiv-1 Subtypes And Drug Resistance Mutations Among Female Sex Workers Varied In Different Cities And Regions Of The Democratic Republic Of Congo, Eun Hee Kwon, Godefroid M. A. Musema, Jessica Boelter, Sydney Townsend, Desire Tshala-Katumbay, Patrick K. Kayembe, John T. West, Charles Wood 2020 University of Nebraska - Lincoln

Hiv-1 Subtypes And Drug Resistance Mutations Among Female Sex Workers Varied In Different Cities And Regions Of The Democratic Republic Of Congo, Eun Hee Kwon, Godefroid M. A. Musema, Jessica Boelter, Sydney Townsend, Desire Tshala-Katumbay, Patrick K. Kayembe, John T. West, Charles Wood

Virology Papers

Background Complex mosaic structures of HIV-1 were found in the Democratic Republic of Congo (DRC). Currently, there is limited information on the circulating HIV-1 strains, the distribution of these strains and antiretroviral (ART) resistant viruses in different regions of the country, and the HIV-1 strains harbored by the high-risk groups like female sex workers (FSW) reported to be the source of recombinant and ART resistant viruses.

Methods Dried Blood Spots (DBS), collected from 325 infected FSWs in ten cities from 2012 DRC HIV/STI Integrated Biological and Behavioral Surveillance Survey, were tested for HIV-1 genotypes and antiretroviral resistance mutations. Regional ...


Perivascular Macrophages In The Neonatal Macaque Brain Undergo Massive Necroptosis After Simian Immunodeficiency Virus Infection, Diana G. Bohannon, Yueying Wang, Colin H. Reinhart, Julian B. Hattler, Jiangtao Luo, Hamid R. Okhravi, Jianshui Zhang, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim 2020 Eastern Virginia Medical School

Perivascular Macrophages In The Neonatal Macaque Brain Undergo Massive Necroptosis After Simian Immunodeficiency Virus Infection, Diana G. Bohannon, Yueying Wang, Colin H. Reinhart, Julian B. Hattler, Jiangtao Luo, Hamid R. Okhravi, Jianshui Zhang, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim

Virology Papers

We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid cell ...


Epstein Barr Virus-Immortalizedblymphocytes Exacerbate Experimental Autoimmune Encephalomyelitis In Xenograft Mice, Pascal Polepole, Alison Bartenslager, Yutong Liu, Thomas M. Petro, Samodha C. Fernando, Luwen Zhang 2020 University of Nebraska - Lincoln

Epstein Barr Virus-Immortalizedblymphocytes Exacerbate Experimental Autoimmune Encephalomyelitis In Xenograft Mice, Pascal Polepole, Alison Bartenslager, Yutong Liu, Thomas M. Petro, Samodha C. Fernando, Luwen Zhang

Virology Papers

Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system. Epstein-Barr virus (EBV) is a causative agent for infectious mononucleosis (IM) that is associated with MS pathogenesis. However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV-infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans and ...


Characterization Of A Speciese Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, David N. Gordon, Theodore C. Pierson, Eric A. Weaver 2020 University of Nebraska - Lincoln

Characterization Of A Speciese Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, David N. Gordon, Theodore C. Pierson, Eric A. Weaver

Virology Papers

The development of a safe and efficacious Zika virus (ZIKV) vaccine remains a global health priority. In our previous work, we developed an Adenovirus vectored ZIKV vaccine using a low-seroprevalent human Adenovirus type 4 (Ad4-prM-E) and compared it to an Ad5 vector (Ad5-prM-E). We found that vaccination with Ad4-prM-E leads to the development of a strong anti-ZIKV T-cell response without eliciting significant anti-ZIKV antibodies, while vaccination with Ad5-prM-E leads to the development of both anti-ZIKV antibody and T-cell responses in C57BL/6 mice. However, both vectors conferred protection against ZIKV infection in a lethal challenge model. Here we continued to ...


Host Transcriptional Response To Persistent Infection With A Live-Attenuated Porcine Reproductive And Respiratory Syndrome Virus Strain, Jayeshbhai Chaudhari, Chia-Sin Liew, Aspen M. Workman, Jean-Jack Riethoven, David J. Steffen, Sarah Vitosh-Sillman, Hiep Vu 2020 University of Nebraska-Lincoln

Host Transcriptional Response To Persistent Infection With A Live-Attenuated Porcine Reproductive And Respiratory Syndrome Virus Strain, Jayeshbhai Chaudhari, Chia-Sin Liew, Aspen M. Workman, Jean-Jack Riethoven, David J. Steffen, Sarah Vitosh-Sillman, Hiep Vu

Virology Papers

Both virulent and live-attenuated porcine reproductive and respiratory syndrome virus (PRRSV) strains can establish persistent infection in lymphoid tissues of pigs. To investigate the mechanisms of PRRSV persistence, we performed a transcriptional analysis of inguinal lymphoid tissue collected from pigs experimentally infected with an attenuated PRRSV strain at 46 days post infection. A total of 6404 differentially expressed genes (DEGs) were detected of which 3960 DEGs were upregulated and 2444 DEGs were downregulated. Specifically, genes involved in innate immune responses and chemokines and receptors associated with T-cell homing to lymphoid tissues were down regulated. As a result, homing of virus-specific ...


Species D Adenoviruses As Oncolytic Viral Vectors, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver 2020 University of Nebraska - Lincoln

Species D Adenoviruses As Oncolytic Viral Vectors, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Virology Papers

Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup ...


Obituary: Thomas Henry Kunz (1938–2020), Allen Kurta, Winifred F. Frick, M. Brock Fenton, Polly Campbell, Gary F. McCracken, Robert M. Timm, Hugh H. Genoways 2020 Eastern Michigan University

Obituary: Thomas Henry Kunz (1938–2020), Allen Kurta, Winifred F. Frick, M. Brock Fenton, Polly Campbell, Gary F. Mccracken, Robert M. Timm, Hugh H. Genoways

Mammalogy Papers: University of Nebraska State Museum

Dr. Thomas Henry Kunz, an internationally recognized expert on the ecology and behavior of bats and Professor at Boston University, passed away on April 13, 2020 in Dedham, Massachusetts, at the age of 81 as the result of complications from COVID-19. “Tom,” to his many friends and colleagues, was born on June 11, 1938 in Independence, Missouri, to William H. and Edna F. (Dornfeld) Kunz. He married Margaret Louise Brown on December 27, 1962 in Faucett, Missouri, Margaret’s hometown. Two children were born to Margaret and Tom—Pamela Kunz (Jeffrey Kwan) and David Kunz (Nicole, née D’Angelo), and ...


Investigating The Mechanism Of The Coronavirus Endoribonuclease In Antagonizing Innate Immune Signaling, Matthew Hackbart 2020 Loyola University Chicago

Investigating The Mechanism Of The Coronavirus Endoribonuclease In Antagonizing Innate Immune Signaling, Matthew Hackbart

Dissertations

Coronaviruses (CoVs) are positive-sense RNa viruses that can emerge from endemic reservoirs and infect zoonotically, causing significant morbidity and mortality. CoVs encode an endoribonuclease (EndoU) that cleaves RNa in biochemical assays, but the target and function of EndoU activity during viral replication was not known. My work focused on characterizing the functions of EndoU during infection. I report that EndoU is an innate immune antagonist. to function as an immune antagonist, EndoU cleaves the 5'-Poly-Uridines from Negative-sense viral RNA, termed PUN RNA, which is the product of polyA-templated RNa synthesis. Using a virus containing an EndoU catalytic-inactive mutation, I ...


Distinct Roles For Carbohydrate And Protein Receptors In Coronavirus Infection, Enya Qing 2020 Loyola University Chicago

Distinct Roles For Carbohydrate And Protein Receptors In Coronavirus Infection, Enya Qing

Dissertations

Coronaviruses (CoVs) are common human and animal pathogens. in humans, four endemic CoV species together account for one third of mild respiratory infections worldwide. More severe and frequently fatal respiratory pathologies are caused by recent CoV outbreaks that resulted from occasional zoonotic spillover from animal CoV reservoirs, namely, SARS-CoV in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019. Because CoVs threaten global health, any chance of relieving CoV's threat on human populations would rely heavily on our understanding of the mechanistic requirements for CoV tropism, whose major determinant is at the level of viral entry. CoVs have evolved to ...


Zika Virus Inactivates Polyamine Catabolism Via Alternative Splicing To Enhance Infection, Marion Lea Graham 2020 Loyola University Chicago

Zika Virus Inactivates Polyamine Catabolism Via Alternative Splicing To Enhance Infection, Marion Lea Graham

Master's Theses

During viral infection, the virus and host must compete for resources inside the cell. One of these resources is polyamines. Polyamines are small, positively charged molecules that are found in all eukaryotic cells. They play a key role in several cellular functions including growth and proliferation, transcription and translation, and membrane stability. Viruses also rely polyamines for productive replication, utilizing them during DNA/RNa polymerization, nucleic acid packaging, and protein synthesis. in response to a virus infecting a host cell, the host cell will begin to regulate polyamine levels as a way to combat the infection. Polyamine levels are regulated ...


Genetic Diversity Of Potassium Ion Channel Proteins Encoded By Chloroviruses That Infect Chlorella Heliozoae, Carter Murry, Irina V. Agarkova, Jayadri S. Ghosh, Fiona C. Fitzgerald, Roger M. Carlson, Brigitte Hertel, Kerri Kukovetz, Oliver Rauh, Gerhard Thiel, James L. Van Etten 2020 University of Nebraska-Lincoln

Genetic Diversity Of Potassium Ion Channel Proteins Encoded By Chloroviruses That Infect Chlorella Heliozoae, Carter Murry, Irina V. Agarkova, Jayadri S. Ghosh, Fiona C. Fitzgerald, Roger M. Carlson, Brigitte Hertel, Kerri Kukovetz, Oliver Rauh, Gerhard Thiel, James L. Van Etten

Virology Papers

Chloroviruses are large, plaque-forming, dsDNA viruses that infect chlorella-like green algae that live in a symbiotic relationship with protists. Chloroviruses have genomes from 290 to 370 kb, and they encode as many as 400 proteins. One interesting feature of chloroviruses is that they encode a potassium ion (K+) channel protein named Kcv. The Kcv protein encoded by SAG chlorovirus ATCV-1 is one of the smallest known functional K+ channel proteins consisting of 82 amino acids. The KcvATCV-1 protein has similarities to the family of two transmembrane domain K+ channel proteins; it consists of two transmembrane -helixes with a pore region ...


How The Cervical Microbiota Contributes To Cervical Cancer Risk In Sub-Saharan Africa, Cameron Klein, Crispin Kahesa, Julius Mwalselage, John T. West, Charles Wood, Peter C. Angeletti 2020 University of Nebraska - Lincoln

How The Cervical Microbiota Contributes To Cervical Cancer Risk In Sub-Saharan Africa, Cameron Klein, Crispin Kahesa, Julius Mwalselage, John T. West, Charles Wood, Peter C. Angeletti

Virology Papers

Despite ongoing efforts, sub-Saharan Africa faces a higher cervical cancer burden than anywhere else in the world. Besides HPV infection, definitive factors of cervical cancer are still unclear. Particular states of the cervicovaginal microbiota and viral infections are associated with increased cervical cancer risk. Notably, HIV infection, which is prevalent in sub-Saharan Africa, greatly increases risk of cervicovaginal dysbiosis and cervical cancer. To better understand and address cervical cancer in sub-Saharan Africa, a better knowledge of the regional cervicovaginal microbiome is required This review establishes current knowledge of HPV, HIV, cervicovaginal infections, and the cervicovaginal microbiota in sub-Saharan Africa. Because ...


Cervico-Vaginal Inflammatory Cytokine And Chemokine Responses To Two Different Siv Immunogens, Nikki P.L. Toledo, Hongzhao Li, Robert W. Omange, Tamara G. Dacoba, Jose Crecente-Campo, Dane Schalk, Mohammad A. Kashem, Eva Rakasz, Nancy Schultz-Darken, Qingsheng Li, James B. Whitney, Maria J. Alonso, Francis A. Plummer, Ma Luo 2020 University of Manitoba, Winnipeg

Cervico-Vaginal Inflammatory Cytokine And Chemokine Responses To Two Different Siv Immunogens, Nikki P.L. Toledo, Hongzhao Li, Robert W. Omange, Tamara G. Dacoba, Jose Crecente-Campo, Dane Schalk, Mohammad A. Kashem, Eva Rakasz, Nancy Schultz-Darken, Qingsheng Li, James B. Whitney, Maria J. Alonso, Francis A. Plummer, Ma Luo

Virology Papers

Studies have shown that vaccine vectors and route of immunization can differentially activate different arms of the immune system. However, the effects of different HIV vaccine immunogens on mucosal inflammation have not yet been studied. Because mucosal sites are the primary route of HIV infection, we evaluated the cervico-vaginal inflammatory cytokine and chemokine levels of Mauritian cynomolgus macaques following immunization and boost using two different SIV vaccine immunogens. The PCS vaccine delivers 12 20-amino acid peptides overlapping the 12 protease cleavage sites, and the Gag/Env vaccine delivers the full Gag and full Env proteins of simian immunodeficiency virus. We ...


A Decade In Review: A Systematic Review Of Universal Influenza Vaccines In Clinical Trials During The 2010 Decade, Brigette N. Corder, Brianna L. Bullard, Gregory Poland, Eric A. Weaver 2020 University of Nebraska - Lincoln

A Decade In Review: A Systematic Review Of Universal Influenza Vaccines In Clinical Trials During The 2010 Decade, Brigette N. Corder, Brianna L. Bullard, Gregory Poland, Eric A. Weaver

Virology Papers

On average, there are 3–5 million severe cases of influenza virus infections globally each year. Seasonal influenza vaccines provide limited protection against divergent influenza strains. Therefore, the development of a universal influenza vaccine is a top priority for the NIH. Here, we report a comprehensive summary of all universal influenza vaccines that were tested in clinical trials during the 2010–2019 decade. Of the 1597 studies found, 69 eligible clinical trials, which investigated 27 vaccines, were included in this review. Information from each trial was compiled for vaccine target, vaccine platform, adjuvant inclusion, clinical trial phase, and results. As ...


Identifying Essential Viral Genes Through Genomic Engineering, Amber Carroll 2020 Western Kentucky University

Identifying Essential Viral Genes Through Genomic Engineering, Amber Carroll

Mahurin Honors College Capstone Experience/Thesis Projects

Bacteria developed resistance to penicillin a mere four years after the groundbreaking antibiotic was first mass produced (Casadevall, 2010). Since then, the development of antibiotic-resistant bacteria has steadily risen, causing millions of difficult to treat infections annually. The challenge is to identify ways to combat these menacing microbes. Bacteriophages are viruses that infect bacteria and can potentially be used to eliminate deadly antibiotic-resistant bacteria. The number of sequenced bacteriophage genomes has increased tremendously over the past 10 years, but little is known about the function of most bacteriophage genes. The purpose of this study was to expand our understanding of ...


Pneumovirus Infections: Understanding Rsv And Hmpv Entry, Replication, And Spread, Jonathan T. Kinder 2020 University of Kentucky

Pneumovirus Infections: Understanding Rsv And Hmpv Entry, Replication, And Spread, Jonathan T. Kinder

Theses and Dissertations--Molecular and Cellular Biochemistry

Pneumoviruses including human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are significant causes of respiratory tract infections globally. Children, elderly, and immunocompromised patients are at the greatest risk for developing severe infections, which can have devastating outcomes. Although these viruses are ubiquitous with significant impacts on human health, there are no antivirals or vaccines available. The only FDA approved therapy is a monoclonal antibody for RSV, given prophylactically during the infectious season, and this treatment is only available for high risk infants. The work presented in this thesis aims to increase our understanding of how these viruses enter, replicate, and ...


Unveiling Crucivirus Diversity By Mining Metagenomic Data, Ignacio de la Higuera, George Kasun, Ellis L. Torrance, Alyssa A. Pratt, Amberlee Maluenda, Jonathan Colombet, Maxime Bisseux, Viviane Ravet, Anisha Dayaram, Daisy Stainton, Simona Kraberger, Peyman Zawar-Reza, Sharyn Goldstien, James V. Briskie, Robyn White, Helen Taylor, Christopher Gomez, David G. Ainley, Jon S. Harding, Rafaela S. Fontenele, Joshua Schreck, Simone Ribeiro, Stephen A. Oswald, Jennifer M. Arnold, François Enault, Arvind Varsani, Kenneth M. Stedman 2020 Portland State University

Unveiling Crucivirus Diversity By Mining Metagenomic Data, Ignacio De La Higuera, George Kasun, Ellis L. Torrance, Alyssa A. Pratt, Amberlee Maluenda, Jonathan Colombet, Maxime Bisseux, Viviane Ravet, Anisha Dayaram, Daisy Stainton, Simona Kraberger, Peyman Zawar-Reza, Sharyn Goldstien, James V. Briskie, Robyn White, Helen Taylor, Christopher Gomez, David G. Ainley, Jon S. Harding, Rafaela S. Fontenele, Joshua Schreck, Simone Ribeiro, Stephen A. Oswald, Jennifer M. Arnold, François Enault, Arvind Varsani, Kenneth M. Stedman

Biology Faculty Publications and Presentations

The discovery of cruciviruses revealed the most explicit example of a common protein homologue between DNA and RNA viruses to date. Cruciviruses are a novel group of circular Rep-encoding single-stranded DNA (ssDNA) (CRESSDNA) viruses that encode capsid proteins that are most closely related to those encoded by RNA viruses in the family Tombusviridae. The apparent chimeric nature of the two core proteins encoded by crucivirus genomes suggests horizontal gene transfer of capsid genes between DNA and RNA viruses. Here, we identified and characterized 451 new crucivirus genomes and 10 capsid-encoding circular genetic elements through de novo assembly and mining of ...


Investigation Of Influenza B Virus Replication Potential In Swine Primary Respiratory Epithelial Cells And Phylodynamic Analysis Of Equine Influenza A H3n8 Viruses, Sunayana Shyam Jandhyala 2020 South Dakota State University

Investigation Of Influenza B Virus Replication Potential In Swine Primary Respiratory Epithelial Cells And Phylodynamic Analysis Of Equine Influenza A H3n8 Viruses, Sunayana Shyam Jandhyala

Electronic Theses and Dissertations

Influenza viruses are respiratory pathogens that cause significant mortality worldwide. The subtype of influenza A virus currently affecting worldwide equine populations is H3N8, leading to epidemics and transboundary pandemics. The individual gene segments of an isolate named A/equine/Montana/9564-1/2015 were phylogenetically characterized. BLASTn search revealed that the polymerase basic protein 1 (PB1), polymerase acidic (PA), hemagglutinin (HA), nucleoprotein (NP), and matrix (M) segments of this H3N8 isolate shared the highest percentage identity to A/equine/Tennessee/29A/2014 (H3N8) and the polymerase basic protein 2 (PB2), neuraminidase (NA), and non-structural protein (NS) segments to A/equine/Malaysia ...


Virus-Induced Changes In Nuclear Proteins And Membranes In Nicotiana Benthamiana Cells, Caleb Mathias 2020 University of Kentucky

Virus-Induced Changes In Nuclear Proteins And Membranes In Nicotiana Benthamiana Cells, Caleb Mathias

Theses and Dissertations--Plant Pathology

Viruses rely on host proteins to complete their life cycles. This results in alterations to normal cell physiology to processes which benefit viral processes such as replication and movement to other cells. This may involve the relocalization of host proteins away from their original subcellular targets to sites which may benefit the virus, a process that is not as well understood as it relates to the nucleus. To identify nuclear proteins that may be involved in such processes, a library of random Nicotiana benthamiana cDNAs were expressed as GFP fusions in a transgenic marker lines expressing a histone 2B:RFP ...


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