Dairy Science Commons^™

A Potent Lassa Virus Antiviral Targets An Arenavirus Virulence Determinant, Ikenna G. Madu, Megan Files, Dima N. Gharaibeh, Amy L. Moore, Kieh-Hoon Jung, Brian B. Gowen, Dongcheng Dai, Kevin F. Jones, Shanthakumar R. Tyavanagimatt, James R. Burgeson, Marcus J. Korth, Kristin M. Bedard, Shawn P. Iadonato, Sean M. Amberg

Animal, Dairy, and Veterinary Science Faculty Publications

Arenaviruses are a significant cause of hemorrhagic fever, an often-fatal disease for which there is no approved antiviral therapy. Lassa fever in particular generates high morbidity and mortality in West Africa, where the disease is endemic, and a recent outbreak in Nigeria was larger and more geographically diverse than usual. We are developing LHF-535, a small-molecule viral entry inhibitor that targets the arenavirus envelope glycoprotein, as a therapeutic candidate for Lassa fever and other hemorrhagic fevers of arenavirus origin. Using a lentiviral pseudotype infectivity assay, we determined that LHF-535 had sub-nanomolar potency against the viral envelope glycoproteins from all Lassa …

Pathogenesis Of Rift Valley Fever Virus Aerosol Infection In Stat2 Knockout Hamsters, Brady T. Hickerson, Jonna B. Westover, Arnaud J. Van Wettere, Johanna D. Rigas, Jinxin Miao, Bettina L. Conrad, Neil E. Motter, Zhongde Wang, Brian B. Gowen

Animal, Dairy, and Veterinary Science Faculty Publications

Rift Valley fever virus (RVFV) is an emerging pathogen capable of causing severe disease in livestock and humans and can be transmitted by multiple routes including aerosol exposure. Several animal models have been developed to gain insight into the pathogenesis associated with aerosolized RVFV infection, but work with these models is restricted to high containment biosafety level (BSL) laboratories limiting their use for antiviral and vaccine development studies. Here, we report on a new RVFV inhalation infection model in STAT2 KO hamsters exposed to aerosolized MP-12 vaccine virus by nose-only inhalation that enables a more accurate delivery and measurement of …

Coitus-Free Sexual Transmission Of Zika Virus In A Mouse Model, Chad S. Clancy, Arnaud J. Van Wettere, John D. Morrey, Justin G. Julander

Animal, Dairy, and Veterinary Science Faculty Publications

Zika virus (ZIKV) is an arboviral infection that may be sexually transmitted. The present study aims to determine if accessory sex glands are a potential source of infectious virus and important in sexual transmission. Male interferon type I receptor knockout (Ifnar^−/−) mice were challenged subcutaneously with a Puerto Rican ZIKV isolate. Reproductive tissues were harvested seven days after viral challenge and artificial insemination fluid derived from epididymis or homogenized accessory sex glands (seminal plasma) was obtained. Naïve interferon type I and II receptor knockout (AG129) females were pretreated with progesterone, and inoculated intravaginally with either epididymal flush or …

A Novel Cancer Syndrome Caused By Kcnq1-Deficiency In The Golden Syrian Hamster, Rong Li, Jinxin Miao, Alexandru-Flaviu Tabaran, M. Gerard O'Sullivan, Kyle J. Anderson, Patricia M. Scott, Zhongde Wang, Robert T. Cormier

Animal, Dairy, and Veterinary Science Faculty Publications

BACKGROUND: The golden Syrian hamster is an emerging model organism. To optimize its use, our group has made the first genetically engineered hamsters. One of the first genes that we investigated is KCNQ1 which encodes for the KCNQ1 potassium channel and also has been implicated as a tumor suppressor gene.

MATERIALS AND METHODS: We generated KCNQ1 knockout (KO) hamsters by CRISPR/Cas9­-mediated gene targeting and investigated the effects of KCNQ1­-deficiency on tumorigenesis.

RESULTS: By 70 days of age seven of the eight homozygous KCNQ1 KOs used in this study began showing signs of distress, and on necropsy six of the seven …

Intramammary Infusion Of Casein Hydrolysate For Involution Of Single Mastitic Mammary Quarters Elevating Cow-Level Somatic Cell Count, Justine Britten, Kerry A. Rood, David J. Wilson

Animal, Dairy, and Veterinary Science Faculty Publications

Mastitis in a single quarter can cause high somatic cell counts (SCC), clinical mastitis, and death in dairy cows. Currently, management of these mastitic quarters presents a problem for the dairy industry. Casein hydrolysate (CH) is an intramammary (IMM) infusion treatment reported to induce mammary involution. The primary objectives of this study were to investigate whether IMM CH treatment of single high SCC quarters, followed by cessation of quarter milk production for the remainder of lactation, was effective in reducing cow–level SCC and whether that quarter resumed milk production following calving. Three treatment groups were used: CH, non-hydrolyzed casein (NHC), …

Early Events In Japanese Encephalitis Virus Infection: Viral Entry, Sang-Im Yun, Young-Min Lee

Animal, Dairy, and Veterinary Science Faculty Publications

Japanese encephalitis virus (JEV), a mosquito-borne zoonotic flavivirus, is an enveloped positive-strand RNA virus that can cause a spectrum of clinical manifestations, ranging from mild febrile illness to severe neuroinvasive disease. Today, several killed and live vaccines are available in different parts of the globe for use in humans to prevent JEV-induced diseases, yet no antivirals are available to treat JEV-associated diseases. Despite the progress made in vaccine research and development, JEV is still a major public health problem in southern, eastern, and southeastern Asia, as well as northern Oceania, with the potential to become an emerging global pathogen. In …

Functional Genomics And Immunologic Tools: The Impact Of Viral And Host Genetic Variations On The Outcome Of Zika Virus Infection, Sang-Im Yun, Byung-Hak Song, Jordan C. Frank, Justin G. Julander, Aaron L. Olsen, Irina A. Polejaeva, Christopher J. Davies, Kenneth L. White, Young-Min Lee

Animal, Dairy, and Veterinary Science Faculty Publications

Zika virus (ZIKV) causes no-to-mild symptoms or severe neurological disorders. To investigate the importance of viral and host genetic variations in determining ZIKV infection outcomes, we created three full-length infectious cDNA clones as bacterial artificial chromosomes for each of three spatiotemporally distinct and genetically divergent ZIKVs: MR-766 (Uganda, 1947), P6-740 (Malaysia, 1966), and PRVABC-59 (Puerto Rico, 2015). Using the three molecularly cloned ZIKVs, together with 13 ZIKV region-specific polyclonal antibodies covering nearly the entire viral protein-coding region, we made three conceptual advances: (i) We created a comprehensive genome-wide portrait of ZIKV gene products and their related species, with several previously …

Immunogenicity And Protection After Vaccination With A Modified Vaccinia Virus Ankara-Vectored Yellow Fever Vaccine In The Hamster Model, Justin G. Julander, Marco Testori, Cédric Cheminay, Ariane Volkmann

Animal, Dairy, and Veterinary Science Faculty Publications

The highly efficacious live-attenuated 17D yellow fever (YF) vaccine is occasionally associated with rare life-threatening adverse events. Modified vaccinia virus Ankara (MVA), a non-replicating poxvirus, has been used as a vaccine platform to safely deliver various antigens. A MVA-based YF vaccine (MVA-BN-YF) was tested with and without a non-mineral oil adjuvant in a hamster model of lethal YF disease and protective efficacy of this vaccine was compared with the 17D vaccine. The vaccine candidate MVA-BN-YF generated a protective response in hamsters infected with YFV that was comparable to protection by the live 17D vaccine. Similar levels of neutralizing antibody were …

A Non-Recoverable Hybridoma Limits The Production Of Monoclonal Antibodies Against Bovine Trophoblast Non-Classical Nc3*00101 Protein, Parveen Parasar, Amanda Wilhelm, William C. Davis, Kenneth L. White, Christopher J. Davies

Animal, Dairy, and Veterinary Science Faculty Publications

The non-classical MHC class I (MHC-Ib) proteins are important modulators of immune system during pregnancy favoring survival of the fetus. Contrary to ubiquitously expressed classical MHC-I proteins, MHC-Ib proteins are oligomorphic, and expressed in specific cell/tissue types thus minimizing maternal immune-mediated rejection of fetal-allograft and a successful pregnancy. A unique characteristic of MHC-Ib glycoproteins is expression of surface and soluble isoforms due to alternative splicing phenomenon. Bovine fetal trophoblast cells, during the third trimester of pregnancy, express non-classical bovine leukocyte antigen class Ib (BoLA-Ib) antigens. BoLA-NC3*00101, is a non-classical class I allele from cattle AH11 …

Urine Volume And Nitrogen Excretion Are Altered By Feeding Birdsfoot Trefoil Compared With Alfalfa In Lactating Dairy Cows, Mohammad Ghelichkhan, Jong-Su Eun, Rachael G. Christensen, Rusty D. Stott, Jennifer W. Macadam

Animal, Dairy, and Veterinary Science Faculty Publications

Legumes that contain condensed tannins may have lower ruminal protein degradation than alfalfa. The present study investigated the effects of feeding birdsfoot trefoil (Lotus corniculatus L.) hay on lactational performance and N utilization and excretion. Eight multiparous Holstein cows in midlactation (150 ± 22.3 d-in-milk) were randomly assigned to 2 treatments [alfalfa hay-based total mixed ration (AHT) or birdsfoot trefoil hay-based total mixed ration (BHT)] in a crossover design with 2 experimental periods. Each experimental period lasted 17 d (14 d of adaptation and 3 d of sampling and total collection). Hays comprised approximately 50% …

Consequences Of In Utero Exposure To Zika Virus In Offspring Of Ag129 Mice, Justin G. Julander, Venkatraman Siddharthan, Albert H. Park, Elizabeth S. Preston, Pranav Mathur, Michael Bertolio, Hong Wang, Katherine Zukor, Arnaud J. Van Wettere, Donal G. Sinex, John D. Morrey

Animal, Dairy, and Veterinary Science Faculty Publications

Zika virus (ZIKV) can cause various diseases in offspring after congenital infection. The purpose of this study was to identify disease phenotypes in pups exposed to ZIKV in utero. Female interferon-α/β, -γ receptor knockout mice (AG129) were infected intraperitoneally with ZIKV 7.5 days’ post coitus (dpc). Viral RNA, antigen and infectious virus were detected in some, but not all, maternal and fetal tissues at various times during gestation. Fetuses of infected dams had significant intrauterine growth restriction (IUGR), which was more pronounced as females neared parturition. Pups born to infected dams were significantly smaller and had significantly shortened skull …

Large Animal Genetic Engineering Summit 2018 Proceedings, Utah State University

Animal, Dairy, and Veterinary Science Faculty Publications

It is our great pleasure to welcome you to the second Large Animal Genetic Engineering (LAGE) Summit in beautiful Park City, Utah. We hope that you enjoy the meeting and take advantage of your free time to get out and see what Park City has to offer. Our objectives for the summit are twofold: (1) to provide updates on genetic engineering technologies, including genome editing, and their biomedical and agricultural applications in academia and industry; and (2) to engage federal agencies, industry representatives and academic researchers in a policy development forum. We hope that this year’s meeting will build on …

Characterization Of An N-Terminal Non-Core Domain Of Rag1 Gene Disrupted Syrian Hamster Model Generated By Crispr Cas9, Jinxin Miao, Baoling Ying, Rong Li, Ann E. Tollefson, Jacqueline F. Spencer, William S.M. Wold, Seok-Hwan Song, Il-Keun Kong, Karoly Toth, Yaohe Wang, Zhongde Wang

Animal, Dairy, and Veterinary Science Faculty Publications

The accumulating evidence demonstrates that Syrian hamsters have advantages as models for various diseases. To develop a Syrian hamster (Mesocricetus auratus) model of human immunodeficiency caused by RAG1 gene mutations, we employed the CRISPR/Cas9 system and introduced an 86-nucleotide frameshift deletion in the hamster RAG1 gene encoding part of the N-terminal non-core domain of RAG1. Histological and immunohistochemical analyses demonstrated that these hamsters (referred herein as RAG1-86nt hamsters) had atrophic spleen and thymus, and developed significantly less white pulp and were almost completely devoid of splenic lymphoid follicles. The RAG1-nt86 hamsters had barely detectable CD3+ and CD4+ T cells. The …

Identification Of Genes Directly Responding To Dlk1 Signaling In Callipyge Sheep, Hui Yu, Jolena N. Waddell, Shihuan Kuang, Ross L. Tellam, Noelle E. Cockett, Christopher A. Bidwell

Animal, Dairy, and Veterinary Science Faculty Publications

Background

In food animal agriculture, there is a need to identify the mechanisms that can improve the efficiency of muscle growth and protein accretion. Callipyge sheep provide excellent machinery since the up-regulation of DLK1 and RTL1 results in extreme postnatal muscle hypertrophy in distinct muscles. The aim of this study is to distinguish the genes that directly respond to DLK1 and RTL1 signaling from the genes that change as the result of muscle specific effects.

Results

The quantitative PCR results indicated that DLK1 expression was significantly increased in hypertrophied muscles but not in non-hypertrophied muscles. However, RTL1 was up-regulated in …

Fetal Demise And Failed Antibody Therapy During Zika Virus Infection Of Pregnant Macaques, Diogo M. Magnani, Thomas F. Rogers, Nicholas J. Maness, Nathan D. Grubaugh, Nathan Beutler, Varian K. Bailey, Lucas Gonzalez-Nieto, Martin J. Gutman, Núria Pedreño-Lopez, Jaclyn M. Kwal, Michael J. Ricciardi, Tereance A. Myers, Justin G. Julander, Rudolf P. Bohm, Margaret H. Gilbert, Faith Schiro, Pyone P. Aye, Robert V. Blair, Mauricio A. Martins, Kathrine P. Falkenstien, Amitinder Kaur, Christine L. Curry, Esper G. Kallas, Ronald C. Desrosiers, Pascal J. Goldschmidt-Clermont, Stephen S. Whitehead, Kristian G. Andersen, Myrna C. Bonaldo, Andrew A. Lackner, Antonito T. Panganiban, Dennis R. Burton, David I. Watkins

Animal, Dairy, and Veterinary Science Faculty Publications

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from …

Syringomyelia In An Adult American Paint Horse, Jacqueline P. Kurz, Kate E. Schoenhals, Gordon A. Hullinger, Arnaud J. Van Wettere

Animal, Dairy, and Veterinary Science Faculty Publications

Syringomyelia is a form of myelodysplasia defined by the formation of one or more fluid-filled cavities within the spinal cord that do not communicate with the central canal. The defect may be congenital or acquired. Clinical signs correlate to the segment of spinal cord affected and include pain, paresis, proprioceptive deficits, alterations in sensation, scoliosis, and autonomic dysfunction. This report describes the clinical and pathologic changes in a case of acquired syringomyelia in a 10-year-old American Paint Horse mare. The horse had a six-week history of progressive proprioceptive deficits in all four limbs, bilateral pelvic limb ataxia, and muscle fasciculations …

Sheep Genome Functional Annotation Reveals Proximal Regulatory Elements Contributed To The Evolution Of Modern Breeds, Marina Naval-Sanchez, Quan Nguyen, Sean Mcwilliam, Laercio R. Porto-Neto, Ross Tellam, Tony Vuocolo, Antonio Reverter, Miguel Perez-Enciso, Rudiger Brauning, Shannon Clarke, Alan Mcculloch, Wahid Zamani, Saeid Naderi, Hamid Reza Rezaei, Francois Pompanon, Pierre Taberlet, Kim C. Worley, Richard A. Gibbs, Donna M. Muzny, Shalini N. Jhangiani, Noelle E. Cockett, Hans Daetwyler, James Kijas

Animal, Dairy, and Veterinary Science Faculty Publications

Domestication fundamentally reshaped animal morphology, physiology and behaviour, offering the opportunity to investigate the molecular processes driving evolutionary change. Here we assess sheep domestication and artificial selection by comparing genome sequence from 43 modern breeds (Ovis aries) and their Asian mouflon ancestor (O. orientalis) to identify selection sweeps. Next, we provide a comparative functional annotation of the sheep genome, validated using experimental ChIP-Seq of sheep tissue. Using these annotations, we evaluate the impact of selection and domestication on regulatory sequences and find that sweeps are significantly enriched for protein coding genes, proximal regulatory elements of genes …

Zika Virus-Induced Acute Myelitis And Motor Deficits In Adult Interferon Αβ/Γ Receptor Knockout Mice, Katherine Zukor, Hong Wang, Venkatraman Siddharthan, Justin G. Julander, John D. Morrey

Animal, Dairy, and Veterinary Science Faculty Publications

Zika virus (ZIKV) has received widespread attention because of its effect on the developing fetus. It is becoming apparent, however, that severe neurological sequelae, such as Guillian-Barrë syndrome (GBS), myelitis, encephalitis, and seizures can occur after infection of adults. This study demonstrates that a contemporary strain of ZIKV can widely infect astrocytes and neurons in the brain and spinal cord of adult, interferon α/β receptor knockout mice (AG129 strain) and cause progressive hindlimb paralysis, as well as severe seizure-like activity during the acute phase of disease. The severity of hindlimb motor deficits correlated with increased numbers of ZIKV-infected lumbosacral spinal …

Comparative Response Of The Hepatic Transcriptomes Of Domesticated And Wild Turkey To Aflatoxin B1, Kent M. Reed, Kristelle M. Mendoza, Juan E. Abrahante, Roger A. Coulombe

Animal, Dairy, and Veterinary Science Faculty Publications

The food-borne mycotoxin aflatoxin B₁ (AFB₁) poses a significant risk to poultry, which are highly susceptible to its hepatotoxic effects. Domesticated turkeys (Meleagris gallopavo) are especially sensitive, whereas wild turkeys (M.g. silvestris) are more resistant. AFB₁ toxicity entails bioactivation by hepatic cytochrome P450s to the electrophilic exo-AFB₁-8,9-epoxide (AFBO). Domesticated turkeys lack functional hepatic GST-mediated detoxification of AFBO, and this is largely responsible for the differences in resistance between turkey types. This study was designed to characterize transcriptional changes induced in turkey livers by AFB₁ , and to contrast the …

Causation Of Acute Flaccid Paralysis By Myelitis And Myositis In Enterovirus-D68 Infected Mice Deficient In Interferon Αβ/Γ Receptor Deficient Mice., John D. Morrey, Hong Wang, Brett L. Hurst, Katherine Zukor, Venkatraman Siddharthan, Arnaud J. Van Wettere, Donal G. Sinex, E. Bart Tarbet

Animal, Dairy, and Veterinary Science Faculty Publications

Enterovirus D68 (EV-D68) caused a large outbreak in the summer and fall of 2014 in the United States. It causes serious respiratory disease, but causation of associated paralysis is controversial, because the virus is not routinely identified in cerebrospinal fluid. To establish clinical correlates with human disease, we evaluated EV-D68 infection in non-lethal paralysis mouse models. Ten-day-old mice lacking interferon responses were injected intraperitoneally with the virus. Paralysis developed in hindlimbs. After six weeks of paralysis, the motor neurons were depleted due to viral infection. Hindlimb muscles were also infected and degenerating. Even at the earliest stage of paralysis, muscles …

Production Of Genetically Engineered Golden Syrian Hamsters By Pronuclear Injection Of The Crispr/Cas9 Complex, Rong Li, Jinxin Miao, Seokhwan Song, Il-Keun Kong, Yaohe Wang, Zhongde Wang

Animal, Dairy, and Veterinary Science Faculty Publications

The pronuclear (PN) injection technique was first established in mice to introduce foreign genetic materials into the pronuclei of one-cell stage embryos. The introduced genetic material may integrate into the embryonic genome and generate transgenic animals with foreign genetic information following transfer of the injected embryos to foster mothers. Following the success in mice, PN injection has been applied successfully in many other animal species. Recently, PN injection has been successfully employed to introduce reagents with gene-modifying activities, such as the CRISPR/Cas9 system, to achieve site-specific genetic modifications in several laboratory and farm animal species. In addition to mastering the …