Life Sciences Commons^™

Treatment Of Yellow Fever Virus With The Ns4b Inhibitor Bdaa And Effects On Rna‐Sensing Innate Immune Pathways In Hamster And Mouse Models, Abbie E. Weight

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Yellow fever (YF) is an acute and often severe disease cause by yellow fever virus (YFV). Although there is an effective vaccine available to prevent YF, there are no antiviral drugs approved to treat the disease, which has a considerable disease burden in endemic areas of South America and Africa. BDAA is an experimental antiviral treatment which has shown efficacy against YFV both in cell culture and when administered before infection in an animal model of disease. BDAA targets the YFV protein NS4B and has two reported mechanisms of action: the primary mechanism of action is the direct inhibition of …

Development, Characterization, And Application Of Two Reporter-Expressing Recombinant Zika Viruses, Sang-Im Yun, Byung-Hak Song, Michael E. Woolley, Jordan C. Frank, Justin G. Julander, Young-Min Lee

Animal, Dairy, and Veterinary Science Faculty Publications

Zika virus (ZIKV), a mosquito-borne transplacentally transmissible flavivirus, is an enveloped virus with an ~10.8 kb plus-strand RNA genome that can cause neurological disease. To facilitate the identification of potential antivirals, we developed two reporter-expressing ZIKVs, each capable of expressing an enhanced green fluorescent protein or an improved luminescent NanoLuc luciferase. First, a full-length functional ZIKV cDNA clone was engineered as a bacterial artificial chromosome, with each reporter gene under the cap-independent translational control of a cardiovirus-derived internal ribosome entry site inserted downstream of the single open reading frame of the viral genome. Two reporter-expressing ZIKVs were then generated by …

A Molecularly Engineered Antiviral Banana Lectin Inhibits Fusion And Is Efficacious Against Influenza Virus Infection In Vivo, Evelyn M. Covés-Datson, Steven R. King, Maureen Legendre, Auroni Gupta, Susana M. Chan, Emily Gitlin, Vikram V. Kulkarni, Jezreel Pantaleón García, Donald F. Smee, Elke Lipka, Scott E. Evans, E. Bart Tarbet, Akira Ono, David M. Markovitz

Animal, Dairy, and Veterinary Science Faculty Publications

There is a strong need for a new broad-spectrum antiinfluenza therapeutic, as vaccination and existing treatments are only moderately effective. We previously engineered a lectin, H84T banana lectin (H84T), to retain broad-spectrum activity against multiple influenza strains, including pandemic and avian, while largely eliminating the potentially harmful mitogenicity of the parent compound. The amino acid mutation at position 84 from histidine to threonine minimizes the mitogenicity of the wild-type lectin while maintaining antiinfluenza activity in vitro. We now report that in a lethal mouse model H84T is indeed nonmitogenic, and both early and delayed therapeutic administration of H84T intraperitoneally are …

Development Of Mouse Models For Respiratory And Neurological Disease Caused By Enterovirus D68 And Evaluation Of Antiviral Therapies, Brett L. Hurst

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Enterovirus D68 (EV-D68) is a virus that normally causes disease in children. While this virus typically causes a respiratory infection, in 2014, a large outbreak of the virus was associated with patients that had paralysis of the arms or legs. Even though the virus was discovered in 1962, little was known about the life cycle of the virus or its ability to cause disease. An animal model of disease was needed to understand how the virus causes disease and to develop antiviral compounds to target the virus life cycle.

We adapted the virus by serial-passage in lung tissues from mice …

Evaluation Of Therapeutics For An Enterovirus 71 Infection In An Ag129 Mouse Model, Christopher Peterson

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Discovered in 1969 in California, enterovirus 71 (EV-71) is a serious cause of disease in young children. It is one of the major causative agents of hand, food, and mouth disease (HFMD), and can produce neurological complications, such as meningitis, encephalitis, and an acute flaccid paralysis. For serious cases, the fatality rate can be up to 26%, almost exclusively in young children.

While the virus was initially discovered in the United States, it was soon detected in the Eastern hemisphere, causing outbreaks in Europe and Asia. The largest outbreak occurred in Taiwan in 2008, with approximately 490,000 cases and 128 …

Development Of An Animal Model For Enterovirus For Evaluation D68 For Screening Of Antiviral Therapies, W. Joseph Evans

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Enterovirus D68 (EV-D68) virus has become more prevalent over the last 15 to 20 years. EV-D68 attacks the respiratory system and can cause severe disease in individuals who have underlying respiratory problems. There have also been reports of individuals with EV-D68 showing signs of neurological system problems and acute flaccid paralysis. Because of the increase in patients with EV-D68 and also the potential for neurological disease, an animal model is needed to study the disease and to evaluate experimental therapies for EV-D68 infection.

To develop the animal model, 4-week old AG129 mice that lack alpha and beta interferon receptors, making …

Modeling Severe Fever With Thrombocytopenia Syndrome Virus Infection In Golden Syrian Hamsters: Importance Of Stat2 In Preventing Disease And Effective Treatment With Favipiravir, Brian B. Gowen, Jonna B. Westover, Jinxin Miao, Arnaud J. Van Wettere, Johanna D. Rigas, Brady T. Hickerson, Kie-Hoon Jung, Rong Li, Bettina L. Conrad, Skot Nielson, Yousuke Furuta, Zhongde Wang

Animal, Dairy, and Veterinary Science Faculty Publications

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease endemic in parts of Asia. The etiologic agent, SFTS virus (SFTSV; family Bunyaviridae, genus Phlebovirus) has caused significant morbidity and mortality in China, South Korea, and Japan, with key features of disease being intense fever, thrombocytopenia, and leukopenia. Case fatality rates are estimated to be in the 30% range, and no antivirals or vaccines are approved for use for treatment and prevention of SFTS. There is evidence that in human cells, SFTSV sequesters STAT proteins in replication complexes, thereby inhibiting type I interferon signaling. Here, we demonstrate …

Development Of A New Tacaribearenavirus Infection Model And Its Use To Explore Antiviral Activity Of A Novelaristeromycin Analog, Brian B. Gowen, M. H. Wong, D. Larson, W. Ye, K. H. Jung, E. J. Sefing, Ramona T. Skirpstunas, Donald F. Smee, John D. Morrey, S. W. Schneller

Animal, Dairy, and Veterinary Science Faculty Publications

Background

A growing number of arenaviruses can cause a devastating viral hemorrhagic fever (VHF) syndrome. They pose a public health threat as emerging viruses and because of their potential use as bioterror agents. All of the highly pathogenic New World arenaviruses (NWA) phylogenetically segregate into clade B and require maximum biosafety containment facilities for their study. Tacaribe virus (TCRV) is a nonpathogenic member of clade B that is closely related to the VHF arenaviruses at the amino acid level. Despite this relatedness, TCRV lacks the ability to antagonize the host interferon (IFN) response, which likely contributes to its inability to …

A New Mouse-Adapted Strain Of Sars-Cov As A Lethal Model Forevaluating Antiviral Agents In Vitro And In Vivo, C. W. Day, R. Baric, S. X. Cai, M. Frieman, Y. Kumaki, John D. Morrey, Donald F. Smee, Dale L. Barnard

Animal, Dairy, and Veterinary Science Faculty Publications

Severe acute respiratory syndrome (SARS) is a highly lethal emerging disease caused by coronavirus SARS-CoV. New lethal animal models for SARS were needed to facilitate antiviral research. We adapted and characterized a new strain of SARS-CoV (strain v2163) that was highly lethal in 5–6 week old BALB/c mice. It had nine mutations affecting 10 amino acid residues. Strain v2163 increased IL-1α, IL-6, MIP-1α, MCP-1, and RANTES in mice, and high IL-6 expression correlated with mortality. The infection largely mimicked human disease, but lung pathology lacked hyaline membrane formation. In vitro efficacy against v2163 was shown with known inhihibitors of SARSCoV …

A Recombinant,Infectious Human Parainfluenza Virus Type 3 Expressing The Enhanced Green Fluorescentprotein For Use In High-Throughput Antiviral Assays, J. P. Roth, J. K. Li, Donald F. Smee, John D. Morrey, Dale L. Barnard

Animal, Dairy, and Veterinary Science Faculty Publications

The ability to rescue an infectious, recombinant, negative-stranded, RNA virus from a cDNA clone, has led to new opportunities for measuring viral replication from a viral expressed reporter gene. In this study, the enhanced green fluorescent protein (EGFP) gene was inserted into the human parainfluenza virus type 3 (HPIV-3) antigenome and a recombinant, infectious virus was rescued. Maximum EGFP expression levels, measured by fluorescence, were seen at day 3. Comparison of a three-day, viral expressed EGFP fluorescence assay to a seven-day, neutral red assay, based on complete cell destruction in virus infected MA-104 cells, yielded Z′-factor values of 0.83 and …

Viramidine, Dale L. Barnard

Animal, Dairy, and Veterinary Science Faculty Publications

No abstract provided.