Life Sciences Commons^™

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 …

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 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 …

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 …

Viramidine, Dale L. Barnard

Animal, Dairy, and Veterinary Science Faculty Publications

No abstract provided.