Microbiology Commons^™

Expanding Mouse-Adapted Yamagata-Like Influenza B Viruses In Eggs Enhances In Vivo Lethality In Balb/C Mice, Matthew J. Pekarek, Erika M. Petro-Turnquist, Adam Rubrum, Richard J. Webby, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouseadapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin–Darby canine kidney cells …

Determinants Of Virus Variation, Evolution, And Host Adaptation, Katherine Latourrette, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Virus evolution is the change in the genetic structure of a viral population over time and results in the emergence of new viral variants, strains, and species with novel biological properties, including adaptation to new hosts. There are host, vector, environmental, and viral factors that contribute to virus evolution. To achieve or fine tune compatibility and successfully establish infection, viruses adapt to a particular host species or to a group of species. However, some viruses are better able to adapt to diverse hosts, vectors, and environments. Viruses generate genetic diversity through mutation, reassortment, and recombination. Plant viruses are exposed to …

Immunogenicity And Protective Efficacy Of A Recombinant Pichinde Viral-Vectored Vaccine Expressing Influenza Virus Hemagglutinin Antigen In Pigs, Sushmita Kumari, Jayeshbhai Chaudhari, Qinfeng Huang, Phillip Gauger, Marcelo Nunes De Almeida, Yuying Liang, Hinh Ly, Hiep Vu

Nebraska Center for Virology: Faculty Publications

Influenza A virus of swine (IAV-S) is an economically important swine pathogen. The IAV-S hemagglutinin (HA) surface protein is the main target for vaccine development. In this study, we evaluated the feasibility of using the recombinant tri-segmented Pichinde virus (rPICV) as a viral vector to deliver HA antigen to protect pigs against IAV-S challenge. Four groups of weaned pigs (T01–T04) were included in the study. T01 was injected with PBS to serve as a non-vaccinated control. T02 was inoculated with rPICV expressing green fluorescence protein (rPICV-GFP). T03 was vaccinated with rPICV expressing the HA antigen of the IAV-S H3N2 strain …

Phylogenetic And Drug-Resistance Analysis Of Hiv-1 Sequences From An Extensive Paediatric Hiv-1 Outbreak In Larkana, Pakistan, Syed Hani Abidi, George Makau Nduva, Dilsha Siddiqui, Wardah Rafaqat, Syed Faisal Mahmood, Amna Rehana Siddiqui, Apsara Ali, Aneeta Hotwani, Rashida Abbas Ferrand, Fatima Mir

Department of Biological & Biomedical Sciences

Introduction: In April 2019, an HIV-1 outbreak among children occurred in Larkana, Pakistan, affecting more than a thousand children. It was assumed that the outbreak originated from a single source, namely a doctor at a private health facility. In this study, we performed subtype distribution, phylogenetic and drug-resistance analysis of HIV-1 sequences from 2019 outbreak in Larkana, Pakistan.
Methods: A total of 401 blood samples were collected between April-June 2019, from children infected with HIV-1 aged 0-15 years recruited into a case-control study to investigate the risk factors for HIV-1 transmission. Partial HIV-1 pol sequences were generated from 344 blood …

Host Cell Responses To Zika Virus Infection, Bikash Ranjan Sahoo

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV) in 2015 as a significant human pathogen causing neurological diseases in infants as well as adults is a serious global health concern. A clear understanding of the mechanisms involved in ZIKV replication in infected host cells as well as the host responses to virus infection are keys to the development of therapeutic strategies against ZIKV. Studies conducted in this dissertation demonstrate that ZIKV infection induces the activation of mTOR signaling cascade that promotes viral protein accumulation and infectious progeny production. While both mTORC1 and mTORC2 are essential for ZIKV replication, the observation that depletion …

The Role Of Interspecies Recombination In The Evolution Of Antibiotic-Resistant Pneumococci, Joshua C. D'Aeth, Mark Pg Van Der Linden, Lesley Mcgee, Herminia De Lencastre, Paul Turner, Jae-Hoon Song, Stephanie W. Lo, Rebecca A. Gladstone, Gps Consortium, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn916-type and Tn1207.1-type elements, conferring tetracycline and macrolide resistance, respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking …

Novel Scalable And Simplified System To Generate Microglia-Containing Cerebral Organoids From Human Induced Pluripotent Stem Cells, Brittany Bodnar, Yongang Zhang, Jinbiao Liu, Yuan Lin, Peng Wang, Zhengyu Wei, Sami Saribas, Yuanjun Zhu, Fang Li, Xu Wang, Wenli Yang, Qingsheng Li, Wen-Zhe Ho, Wenhui Hu

Nebraska Center for Virology: Faculty Publications

Human cerebral organoid (CO) is a three-dimensional (3D) cell culture system that recapitulates the developing human brain. While CO has proved an invaluable tool for studying neurological disorders in a more clinically relevant matter, there have still been several shortcomings including CO variability and reproducibility as well as lack of or underrepresentation of certain cell types typically found in the brain. As the technology to generate COs has continued to improve, more efficient and streamlined protocols have addressed some of these issues. Here we present a novel scalable and simplified system to generate microglia-containing CO (MCO). We characterize the cell …

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

Prevalence And Risk Factors Associated With Multi-Drug Resistant Organisms (Mdro) Carriage Among Pediatric Patients At The Time Of Admission In A Tertiary Care Hospital Of A Developing Country. A Cross-Sectional Study, Sonia Qureshi, Noshi Maria, Mohammad Zeeshan, Seema Irfan, Farah Naz Qamar

Department of Paediatrics and Child Health

Background: The rise of Multidrug-resistant organisms (MDROs) poses a considerable burden on the healthcare systems, particularly in low-middle income countries like Pakistan. There is a scarcity of data on the carriage of MDRO particularly in the pediatrics population therefore, we aimed to determine MDRO carriage in pediatric patients at the time of admission to a tertiary care hospital in Karachi, Pakistan, and to identify the risk factors associated with it.
Methods: A cross-sectional study conducted at the pediatric department of Aga Khan University Hospital (AKUH) from May to September 2019 on 347 children aged 1-18 years. For identification of MDRO …

Draft Genome Sequences Of 13 Vibrio Cholerae Strains From The Rio Grande Delta, Jeffrey W. Turner, Jorge Duran-Gonzalez, David A. Laughlin, Daniel Unterweger, David Silva, Boris Ermolinsky, Stefan Pukatzki, Daniele Provenzano

Publications and Research

Vibrio cholerae is the etiologic agent of cholera, an acute and often fatal diarrheal disease that affects millions globally. We report the draft genome sequences of 13 non-O1/O139 V. cholerae strains isolated from the Rio Grande Delta in Texas. These genomes will aid future analyses of environmental serovars.

Genome Sequence Of A Virulent African Swine Fever Virus Isolated In 2020 From A Domestic Pig In Northern Vietnam, Quang Lam Truong, Thi Lan Nguyen, Thi Hoa Nguyen, Jishu Shi, Hiep Lai Xuan Vu, Thi Lan Huong Lai, Van Giap Nguyen

Nebraska Center for Virology: Faculty Publications

This study reports the genome sequence of an isolated African swine fever (ASF) virus (VNUA-ASFV-05L1/HaNam) obtained at the fourth passage on pulmonary alveolar macrophages. The virus was isolated during a typical acute ASF outbreak in pigs in a northern province of Vietnam in 2020.

Codon Bias Can Determine Sorting Of A Potassium Channel Protein, Anja J. Engel, Marina Kithil, Markus Langhans, Oliver Rauh, Matea Cartolano, James L. Van Etten, Anna Moroni, Gerhard Thiel

Nebraska Center for Virology: Faculty Publications

Due to the redundancy of the genetic code most amino acids are encoded by multiple synonymous codons. It has been proposed that a biased frequency of synonymous codons can affect the function of proteins by modulating distinct steps in transcription, translation and folding. Here, we use two similar prototype K⁺ channels as model systems to examine whether codon choice has an impact on protein sorting. By monitoring transient expression of GFP-tagged channels in mammalian cells, we find that one of the two channels is sorted in a codon and cell cycle-dependent manner either to mitochondria or the secretory pathway. …

Identification Of A Chlorovirus Pbcv-1 Protein Involved In Degrading The Host Cell Wall During Virus Infection, Irina V. Agarkova, Leslie C. Lane, David D. Dunigan, Cristian F. Quispe, Garry A. Duncan, Elad Milrot, Abraham Minsky, Ahmed Esmael, Jayadri S. Ghosh, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Chloroviruses are unusual among viruses infecting eukaryotic organisms in that they must, like bacteriophages, penetrate a rigid cell wall to initiate infection. Chlorovirus PBCV-1 infects its host, Chlorella variabilis NC64A by specifically binding to and degrading the cell wall of the host at the point of contact by a virus-packaged enzyme(s). However, PBCV-1 does not use any of the five previously characterized virus-encoded polysaccharide degrading enzymes to digest the Chlorella host cell wall during virus entry because none of the enzymes are packaged in the virion. A search for another PBCV-1-encoded and virion-associated protein identified protein A561L. The fourth domain …

Presence Of Antibody-Dependent Cellular Cytotoxicity (Adcc) Against Sars-Cov-2 In Covid-19 Plasma, For Yue Tso, Salum J. Lidenge, Lisa K. Poppe, Phoebe B. Pena, Sara R. Privatt, Sydney J. Bennett, John R. Ngowi, Julius Mwaiselage, Michael Belshan, Jacob A. Siedlik, Morgan A. Raine, Juan B. Ochoa, Julia Garcia-Diaz, Bobby Nossaman, Lyndsey Buckner, W Mark Roberts, Matthew J. Dean, Augusto C. Ochoa, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background Neutralizing-antibody (nAb) is the major focus of most ongoing COVID-19 vaccine trials. However, nAb response against SARS-CoV-2, when present, decays rapidly. Given the myriad roles of antibodies in immune responses, it is possible that antibodies could also mediate protection against SARS-CoV-2 via effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), which we sought to explore here. Methods Plasma of 3 uninfected controls and 20 subjects exposed to, or recovering from, SARS CoV-2 infection were collected from U.S. and sub-Saharan Africa. Immunofluorescence assay was used to detect the presence of SARS-CoV-2 specific IgG antibodies in the plasma samples. SARS-CoV-2 specific …

Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Indian Institute Of Technology Indore, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV), a mosquito-transmitted Flavivirus, emerged in the last decade causing serious diseases and affecting human health globally. Currently, no licensed vaccines or antivirals are available to combat ZIKV, although several vaccine candidates are in the pipeline. In recent years, the presence of non-canonical G-quadruplex (GQ) secondary structures in viral genomes has ignited significant attention as potential targets for antiviral strategy. In this study, we identified several novel conserved potential GQ structures by analyzing published ZIKV genome sequences using an in-house algorithm. Biophysical and biochemical analysis of the RNA sequences containing these potential GQ sequences suggested the existence of …

High Prevalence Of Pre-Existing Serological Cross-Reactivity Against Severe Acute Respiratory Syndrome Coronavirus-2 (Sars-Cov-2) In Sub-Saharan Africa, For Yue Tso, Salum J. Lidenge, Phoebe B. Peña, Ashley A. Clegg, John R. Ngowi, Julius Mwaiselage, Owen Ngalamika, Peter Julius, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA.

Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by …

Characterizing The Physiology And Genetics Of Contact Dependent Growth Inhibiton Systems In Burkholderia Species, Alice Elizabeth Oates

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Contact-dependent growth inhibition (CDI) systems mediate interbacterial competition. The genes encoding these systems are widespread among Gram-negative bacteria, including Burkholderia pathogens. CDI systems of Burkholderia species are composed of two-partner secretion pathway proteins and function to deliver the toxic C-terminus of a polymorphic surface-exposed exoprotein BcpA (Burkholderia CDI protein A) to the cytoplasm of neighboring recipient bacteria upon cell-cell contact. Specific outer and inner membrane proteins facilitate BcpA translocation both out of the donor bacterium and into the recipient cell cytoplasm. Most Burkholderia species-specific CDI translocation factors in recipient cells are unknown. BcpA intoxication functions as a mechanism by …

High Prevalence Of Pre-Existing Serological Cross-Reactivity Against Severe Acute Respiratory Syndrome Coronavirus-2 (Sars- Cov-2) In Sub-Saharan Africa, For Yue Tso, Salum Lidenge, Phoebe B. Peña, Ashley A. Clegg, John R. Ngowi, Julius Mwaiselage, Owen Ngalamika, Peter Julius, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA.

Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by …

The 20th Anniversary Meeting Of The Rocky Mountain Virology Association, Joel Rovnak, Laura A. St Clair, Carley Mcalister, Chinemerem P. Ogbu, Jessica Smolenske, Randall J. Cohrs, Rushika Perera

Nebraska Center for Virology: Faculty Publications

Due to the COVID-19 pandemic and multiple devastating forest fires, the 2020 meeting of the Rocky Mountain Virology Association was held virtually. The three-day gathering featured talks describing recent advances in virology and prion research. The keynote presentation described the measles virus paradox of immune suppression and life-long immunity. Special invited speakers presented information concerning visualizing antiviral effector cell biology in mucosal tissues, uncovering the T-cell tropism of Epstein-Barr virus type 2, a history and current survey of coronavirus spike proteins, a summary of Zika virus vaccination and immunity, the innate immune response to flavivirus infections, a discussion concerning prion …

Chlorovirus Pbcv-1 Multidomain Protein A111/114r Has Three Glycosyltransferase Functions Involved In The Synthesis Of Atypical N-Glycans, Eric Noel, Anna Notaro, Immacolata Speciale, Garry A. Duncan, Cristina De Castro, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life. All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars. A combination of ge- netic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each. Here, in addition to in silico sequence …

Strategies Targeting Hemagglutinin As A Universal Influenza Vaccine, Brianna L. Bullard, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Influenza virus has significant viral diversity, both through antigenic drift and shift, which makes development of a vaccine challenging. Current influenza vaccines are updated yearly to in- clude strains predicted to circulate in the upcoming influenza season, however this can lead to a mismatch which reduces vaccine efficacy. Several strategies targeting the most abundant and im- munogenic surface protein of influenza, the hemagglutinin (HA) protein, have been explored. These strategies include stalk-directed, consensus-based, and computationally derived HA immunogens. In this review, we explore vaccine strategies which utilize novel antigen design of the HA protein to improve cross-reactive immunity for development …

Zika Virus Infection Induces Endoplasmic Reticulum Stress And Apoptosis In Placental Trophoblasts, Philma Glora Muthuraj, Prakask K. Sahoo, Madison Kraus, Taylor Bruett, Arun S. Annamalai, Aryamav Pattnaik, Asit K. Pattnaik, Siddappa N. Byrareddy, Sathish Kumar Natarajan

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV) infection to a pregnant woman can be vertically transmitted to the fetus via the placenta leading to Congenital Zika syndrome. This is characterized by microcephaly, retinal defects, and intrauterine growth retardation. ZIKV induces placental trophoblast apoptosis leading to severe abnormalities in the growth and development of the fetus. However, the molecular mechanism behind ZIKV-induced apoptosis in placental trophoblasts remains unclear. We hypothesize that ZIKV infection induces endoplasmic reticulum (ER) stress in the trophoblasts, and sustained ER stress results in apoptosis. HTR-8 (HTR-8/SVneo), a human normal immortalized trophoblast cell and human choriocarcinoma-derived cell lines (JEG-3 and JAR) were …

Acute Ischemic Stroke As The Presenting Feature Of Covid-19 In The Young And Pregnant, Nermila A. Ballmick, Jiri F. Kubac, Hossein Akhondi

HCA Healthcare Journal of Medicine

Introduction: Coronavirus disease (COVID-19) is an emerging and rapidly evolving public health issue that has become globally widespread and an overwhelming pandemic. Clinical manifestations of the disease include asymptomatic carrier states, acute respiratory distress syndrome, and even multiorgan dysfunction. Here, we present a unique and rare case of an acute ischemic stroke (AIS) in an asymptomatic pregnant woman with no predisposing medical illnesses.

Discussion: An 18-year-old G2P1 African American woman at 7 weeks gestational age with no significant medical or family history presenting to the Emergency Department during the initial phases of the pandemic with complaints of new onset left …

A Functional K+ Channel From Tetraselmis Virus 1, A Member Of The Mimiviridae, Kerri Kukovetz, Brigitte Hertel, Christopher R. Schvarcz, Andrea Saponaro, Mirja Manthey, Ulrike Burk, Timo Greiner, Grieg F. Steward, James L. Van Etten, Anna Moroni, Gerhard Thiel, Oliver Rauh

Nebraska Center for Virology: Faculty Publications

Potassium ion (K+) channels have been observed in diverse viruses that infect eukaryotic marine and freshwater algae. However, experimental evidence for functional K+ channels among these alga-infecting viruses has thus far been restricted to members of the family Phycodnaviridae, which are large, double-stranded DNA viruses within the phylum Nucleocytoviricota. Recent sequencing projects revealed that alga-infecting members of Mimiviridae, another family within this phylum, may also contain genes encoding K+ channels. Here we examine the structural features and the functional properties of putative K+ channels from four cultivated members of Mimiviridae. While all four proteins contain variations …

Defining The Proteolytic Landscape During Enterovirus Infection., Mohsan Saeed, Sebastian Kapell, Nicholas T Hertz, Xianfang Wu, Kierstin Bell, Alison W Ashbrook, Milica Tesic Mark, Henry A Zebroski, Maxwell L Neal, Malin Flodström-Tullberg, Margaret R Macdonald, John D Aitchison, Henrik Molina, Charles M Rice

Articles, Abstracts, and Reports

Viruses cleave cellular proteins to remodel the host proteome. The study of these cleavages has revealed mechanisms of immune evasion, resource exploitation, and pathogenesis. However, the full extent of virus-induced proteolysis in infected cells is unknown, mainly because until recently the technology for a global view of proteolysis within cells was lacking. Here, we report the first comprehensive catalog of proteins cleaved upon enterovirus infection and identify the sites within proteins where the cleavages occur. We employed multiple strategies to confirm protein cleavages and assigned them to one of the two enteroviral proteases. Detailed characterization of one substrate, LSM14A, a …

Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding

Electronic Theses and Dissertations

Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …

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

Nebraska Center for Virology: Faculty Publications

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 …

Characterization Of A Plasmid-Based Dna Vaccine For Simian Immunodeficiency Virus, Priya Sanipara

Honors Theses

Described as one of the world’s worst pandemics, HIV (Human Immunodeficiency Virus) infects millions of people each year and is the cause for AIDS (Acquired Immunodeficiency Syndrome). Despite the development of vaccines for numerous infectious diseases such as polio, small pox, and influenza, a vaccine for HIV remains elusive due to the virus’s high mutation rate and ability to evade the immune system. HIV causes depletion of CD4+ lymphocytes, resulting in a weakened immune system. However, the development of a plasmid-based DNA vaccine approach may help revolutionize vaccine development for HIV due to its ability to confer cellular and humoral …

Elucidating The Regulon Of A Fur-Like Protein In Mycobacterium Avium Subsp. Paratuberculosis (Map), Fernanda Miyagaki Shoyama, Taveesak Janetanakit, John P. Bannantine, Raul G. Barletta, Srinand Sreevatsan

Nebraska Center for Virology: Faculty Publications

Intracellular iron concentration is tightly regulated to maintain cell viability. Iron plays important roles in electron transport, nucleic acid synthesis, and oxidative stress. A Mycobacterium avium subsp. paratuberculosis (MAP)-specific genomic island carries a putative metal transport operon that includes MAP3773c, which encodes a Fur-like protein. Although well characterized as a global regulator of iron homeostasis in multiple bacteria, the function of Fur (ferric uptake regulator) in MAP is unknown as this organism also carries IdeR (iron dependent regulator), a native iron regulatory protein specific to mycobacteria. Computational analysis using PRODORIC identified 23 different pathways involved in respiration, metabolism, and virulence …

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

Nebraska Center for Virology: Faculty Publications

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 characterize …