Life Sciences Commons^™

Memantine Treatment Reduces The Incidence Of Flaccid Paralysis In A Zika Virus Mouse Model Of Temporary Paralysis With Similarities To Guillain-Barré Syndrome, Venkatraman Siddharthan, Hong Wang, Alexandre Lr De Oliveria, Xin Dai, John D. Morrey

Animal, Dairy, and Veterinary Science Faculty Publications

Clinical evidence suggests that Zika virus contributes to Guillain-Barré syndrome that causes temporary paralysis. We utilized a recently described Zika virus mouse model of temporary flaccid paralysis to address the hypothesis that treatment with an N-methyl-D-aspartate receptor antagonist, memantine, can reduce the incidence of paralysis. Aged interferon alpha/beta-receptor knockout mice were used because of their sublethal susceptibility to Zika virus infection. Fifteen to twenty-five percent of mice infected with a Puerto Rico strain of Zika virus develop acute flaccid paralysis beginning at days 8–9 and peaked at days 10–12. Mice recover from paralysis within a week of onset. In …

Association Between Single Nucleotide Polymorphisms In Sirt1 And Sirt2 Loci And Growth In Tibetan Sheep, Lin-Sheng Gui, Sayed Haidar Abbas Raza, Li Zhou, Matthew Garcia, Ayman Hassan Abd El-Aziz, Dawei Wei, Shengzhen Hou, Jianlei Jia, Zhiyou Wang

Animal, Dairy, and Veterinary Science Faculty Publications

Silent information regulator 1 and 2 (SIRT1, 2) were NAD+-dependent histone or non-histone deacetylase, which emerged as key metabolic sensors in several tissues of mammals. In the present study, the search for polymorphisms within the ovine SIRT1 and SIRT2 loci as well as association analyses between SNPs and growth-related traits were performed in Tibetan sheep. To determine the expression pattern of SIRT1 and SIRT2 genes in Tibetan sheep, the quantitative real-time polymerase chain reaction (qPCR) analysis revealed that those two genes were widely expressed in diverse tissues. Expression of SIRT1 was less in abomasum of lamb, whereas it …

Characterization Of A Novel Stat 2 Knock Out Hamster Model Of Crimean Congo Hemorrhagic Fever Virus Pathogenesis, Charlene Ranadheera, Emelissa J. Valcourt, Bryce M. Warner, Guillaume Poliquin, Kyle Rosenke, Kathy Frost, Kevin Tierney, Greg Saturday, Jinxin Miao, Jonna B. Westover, Brian B. Gowen, Stephanie Booth, Heinz Feldmann, Zhongde Wang, David Safronetz

Animal, Dairy, and Veterinary Science Faculty Publications

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen causing a febrile illness in humans, which can progress to hemorrhagic manifestations, multi-organ failure, and death. Current mouse models of CCHFV infection reliably succumb to virus challenge but vary in their ability to reflect signs of disease similar to humans. In this study, we established a signal transducer and activator of transcription 2 (STAT2) knockout hamster model to expand the repertoire of animal models of CCHFV pathogenesis that can be used for therapeutic development. These hamsters demonstrated a systemic and lethal disease in response to infection. Hallmarks of human …

Raman Spectroscopy Characterization Extracellular Vesicles From Bovine Placenta And Peripheral Blood Mononuclear Cells, Han Zhang, Ana Caroline Silva, Wei Zhang, Heloisa M. Rutigliano, Anhong Zhou

Animal, Dairy, and Veterinary Science Faculty Publications

Placenta-derived extracellular vesicles (EVs) are involved in communication between the placenta and maternal immune cells possibly leading to a modulation of maternal T-cell signaling components. The ability to identify EVs in maternal blood may lead to the development of diagnostic and treatment tools for pregnancy complications. The objective of this work was to differentiate EVs from bovine placenta (trophoblast) and peripheral blood mononuclear cells (PBMC) by a label-free, non-invasive Raman spectroscopy technique. Extracellular vesicles were isolated by ultracentrifugation. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) were applied to verify the presence and the size distribution of EVs. Raman …

Comparison Of In Vitro Inactivation Of Sars Cov-2 With Hydrogen Peroxide And Povidone-Iodine Oral Antiseptic Rinses, Avinash S. Bidra, Jesse S. Pelletier, Jonna B. Westover, Samantha Frank, Seth M. Brown, Belachew Tessema

Animal, Dairy, and Veterinary Science Faculty Publications

Purpose

To evaluate the in vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with hydrogen peroxide (H2O2) and povidone‐iodine (PVP‐I) oral antiseptic rinses at clinically recommended concentrations and contact times.

Materials and Methods

SARS‐CoV‐2, USA‐WA1/2020 strain virus stock was prepared prior to testing by growing in Vero 76 cells. The culture media for prepared virus stock was minimum essential medium (MEM) with 2% fetal bovine serum (FBS) and 50 µg/mL gentamicin. Test compounds consisting of PVP‐I oral rinse solutions and H2O2 aqueous solutions were mixed directly with the virus solution so that the final concentration was 50% of …

Rapid In-Vitro Inactivation Of Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Using Povidone-Iodine Oral Antiseptic Rinse, Avinash S. Bidra, Jesse S. Pelletier, Jonna B. Westover, Samantha Frank, Seth M. Brown, Belachew Tessema

Animal, Dairy, and Veterinary Science Faculty Publications

Purpose

To investigate the optimal contact time and concentration for viricidal activity of oral preparation of povidone‐iodine (PVP‐I) against SARS‐CoV‐2 (‘corona virus’) to mitigate the risk and transmission of the virus in the dental practice.

Materials and Methods

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) USA‐WA1/2020 strain, virus stock was tested against oral antiseptic solutions consisting of aqueous povidone‐iodine (PVP‐I) as the sole active ingredient. The PVP‐I was tested at diluted concentrations of 0.5%, 1%, and 1.5%. Test media without any virus was added to 2 tubes of the compounds to serve as toxicity and neutralization controls. Ethanol (70%) …

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 …

Influence Of Total Western Diet On Docosahexaenoic Acid Suppression Of Silica-Triggered Lupus Flaring In Nzbwf1 Mice, Kristen N. Gilley, Kathryn A. Wierenga, Preeti S. Chauhaun, James G. Wagner, Ryan P. Lewandowski, Elizbeth A. Ross, A. L. Lock, Jack R. Harkema, Abby D. Benninghoff, James J. Pestka

Animal, Dairy, and Veterinary Science Faculty Publications

Lupus is a debilitating multi-organ autoimmune disease clinically typified by periods of flare and remission. Exposing lupus-prone female NZBWF1 mice to crystalline silica (cSiO₂), a known human autoimmune trigger, mimics flaring by inducing interferon-related gene (IRG) expression, inflammation, ectopic lymphoid structure (ELS) development, and autoantibody production in the lung that collectively accelerate glomerulonephritis. cSiO₂-triggered flaring in this model can be prevented by supplementing mouse diet with the ω-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). A limitation of previous studies was the use of purified diet that, although optimized for rodent health, does not reflect the …

Evolutionary Selection Against Short Nucleotide Sequences In Viruses And Their Related Hosts, Yoram Zarai, Zohar Zafrir, Bunpote Siridechadilok, Amporn Suphatrakul, Modi Roopin, Justin G. Julander, Tamir Tuller

Animal, Dairy, and Veterinary Science Faculty Publications

Viruses are under constant evolutionary pressure to effectively interact with the host intracellular factors, while evading its immune system. Understanding how viruses co-evolve with their hosts is a fundamental topic in molecular evolution and may also aid in developing novel viral based applications such as vaccines, oncologic therapies, and anti-bacterial treatments. Here, based on a novel statistical framework and a large-scale genomic analysis of 2,625 viruses from all classes infecting 439 host organisms from all kingdoms of life, we identify short nucleotide sequences that are under-represented in the coding regions of viruses and their hosts. These sequences cannot be explained …

Theoretical Risk Of Genetic Reassortment Should Not Impede Development Of Live, Attenuated Rift Valley Fever (Rvf) Vaccines Commentary On The Draft Who Rvf Target Product Profile, Thomas P. Monath, Jeroen Kortekaas, Douglas M. Watts, Rebecca C. Christofferson, Angelle Desiree Labeaud, Brian B. Gowen, Clarence J. Peters, Darci R. Smith, Robert Swanepoel, John C. Morrill, Thomas G. Ksiazek, Phillip R. Pittman, Brian H. Bird, George Bettinger

Animal, Dairy, and Veterinary Science Faculty Publications

In November 2019, The World Health Organization (WHO) issued a draft set of Target Product Profiles (TPPs) describing optimal and minimally acceptable targets for vaccines against Rift Valley fever (RVF), a Phlebovirus with a three segmented genome, in both humans and ruminants. The TPPs contained rigid requirements to protect against genomic reassortment of live, attenuated vaccines (LAVs) with wild-type RVF virus (RVFV), which place undue constraints on development and regulatory approval of LAVs. We review the current LAVs in use and in development, and conclude that there is no evidence that reassortment between LAVs and wild-type RVFV has occurred during …

Consumption Of The Total Western Diet Promotes Colitis And Inflammation-Associated Colorectal Cancer In Mice, Abby D. Benninghoff, Korry J. Hintze, Stephany P. Monsanto, Daphne Michelle Rodriguez Jimenez, Ashli H. Hunter, Sumira Phatak, James J. Pestka, Arnaud J. Van Wettere, Robert E. Ward

Animal, Dairy, and Veterinary Science Faculty Publications

Consumption of a Western type diet is a known risk factor for colorectal cancer. Our group previously developed the total Western diet (TWD) for rodents with energy and nutrient profiles that emulate a typical Western diet. In this study, we tested the hypothesis that consumption of the TWD would enhance colitis, delay recovery from gut injury and promote colon tumorigenesis. In multiple experiments using the azoxymethane + dextran sodium sulfate or Apc^Min/+ mouse models of colitis-associated colorectal carcinogenesis (CAC), we determined that mice fed TWD experienced more severe and more prolonged colitis compared to their counterparts fed the standard …

Guinea Pig Transferrin Receptor 1 Mediates Cellular Entry Of Junín Virus And Other Pathogenic New World Arenaviruses, Brady T. Hickerson, Jonna B. Westover, Zhongde Wang, Young-Min Lee, Brian B. Gowen

Animal, Dairy, and Veterinary Science Faculty Publications

Several clade B New World arenaviruses (NWAs) can cause severe and often fatal hemorrhagic fever, for which preventive and therapeutic measures are severely limited. These NWAs use human transferrin receptor 1 (hTfR1) as a host cell receptor for virus entry. The most prevalent of the pathogenic NWAs is Junín virus (JUNV), the etiological agent of Argentine hemorrhagic fever. Small animal models of JUNV infection are limited because most laboratory rodent species are refractory to disease. Only guinea pigs are known to develop disease following JUNV infection, but the underlying mechanisms are not well characterized. In the present study, we demonstrate …

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 …