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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 Aug 2020

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 …


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 May 2020

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 …


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 Apr 2020

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 …


Human Polyclonal Antibodies Produced From Transchromosomal Bovine Provides Prophylactic And Therapeutic Protections Against Zika Virus Infection In Stat2 Ko Syrian Hamsters, Venkatraman Siddharthan, Jinxin Miao, Arnaud J. Van Wettere, Rong Li, Hua Wu, Eddie Sullivan, Jinan Jiao, Jay W. Hooper, David Safronetz, John D. Morrey, Justin G. Julander, Zhongde Wang Jan 2019

Human Polyclonal Antibodies Produced From Transchromosomal Bovine Provides Prophylactic And Therapeutic Protections Against Zika Virus Infection In Stat2 Ko Syrian Hamsters, Venkatraman Siddharthan, Jinxin Miao, Arnaud J. Van Wettere, Rong Li, Hua Wu, Eddie Sullivan, Jinan Jiao, Jay W. Hooper, David Safronetz, John D. Morrey, Justin G. Julander, Zhongde Wang

Animal, Dairy, and Veterinary Science Faculty Publications

Zika virus (ZIKV) infection can cause severe congenital diseases, such as microcephaly, ocular defects and arthrogryposis in fetuses, and Guillain–Barré syndrome in adults. Efficacious therapeutic treatments for infected patients, as well as prophylactic treatments to prevent new infections are needed for combating ZIKV infection. Here, we report that ZIKV-specific human polyclonal antibodies (SAB-155), elicited in transchromosomal bovine (TcB), provide significant protection from infection by ZIKV in STAT2 knockout (KO) golden Syrian hamsters both prophylactically and therapeutically. These antibodies also prevent testicular lesions in this hamster model. Our data indicate that antibody-mediated immunotherapy is effective in treating ZIKV infection. Because suitable …


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 Aug 2018

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 …


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 Apr 2018

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 …


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 Feb 2018

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 …


Small-Animal Models Of Zika Virus, Justin G. Julander, Venkatraman Siddharthan Dec 2017

Small-Animal Models Of Zika Virus, Justin G. Julander, Venkatraman Siddharthan

Animal, Dairy, and Veterinary Science Faculty Publications

Zika virus (ZIKV) infection can result in serious consequences, including severe congenital manifestations, persistent infection in the testes and neurologic sequelae. After a pandemic emergence, the virus has spread to much of the new world and has been introduced to many countries outside of endemic areas as infected travelers return to their home countries. Rodent models have been important in gaining a better understanding of the wide range of disease etiologies associated with ZIKV infection and for the initial phase of developing countermeasures to prevent or treat viral infections. We discuss herein the advantages and disadvantages of small animal models …