Veterinary Medicine Newsletter – Summer 2020

Virginia-Maryland College of Veterinary Medicine College of Agriculture and Natural Resources

ISSUE 5 │ SUMMER 2020 │FEARLESS IDEAS

Dear friends and colleagues, While 2020 has started in an unconventional way due to the COVID-19 outbreak, I am very proud of the progress and hard work put forth by our faculty, staff, and students. We have continued to move forward with successful adaptations to this new way of life in our department and managed to achieve numerous goals during these unprecedented times. I would like to briefly highlight some of these achievements with you.

In collaboration with the College of Agriculture and Natural Resources we launched our new and improved website. We began a search for two new faculty members who will specialize in Avian Influenza and Antimicrobial Resistance. We have also Initiated some facility upgrades, including a lab floor renovation and an updated building security system.

In response to the COVID-19 pandemic the department is actively developing anti-viral therapeutics and vaccines. We have adapted our facility to allow for social distancing and safe return to work practices.

Provided written and adopted guidelines and protocols. Completed technology and accessibility modifications to allow faculty and staff to telework.

I want to thank the strong support of Dean Craig Beyrouty, outgoing-Interim Dean Gregory Daniel, incoming Dean Daniel Givens and all the members of our college and department for their dedication and hard work.

Sincerely,

Xiaoping Zhu, DVM, Ph.D., Professor Associate Dean and Department Chair

Awards & Recognitions

Ishita Roy Chowdhury, of Dr. Belov’s Lab, was selected as a recipient for the American Society for Virology Student Travel Award for her abstract entitled "Newcastle disease virus vectors coexpressing HA and NA proteins protect poultry against highly pathogenic H7N8 avian influenza virus” which was accepted to the 39th Annual Meeting of the American Society for Virology.

Shaoli Lin, of Dr. Zhang's lab, has been awarded the Ann G. Wylie Dissertation Fellowship during the 2020-2021 academic year. The Ann G. Wylie Dissertation Fellowship supports students with excellent qualifications who are in the latter stages of writing their dissertations.

Dr. Daniel Nelson is a Finalist, Inventor of the Year, University of Maryland.

Dr. Nathaniel Tablante has been awarded the 2020 UME Extension Excellence Award from the College of Agriculture and Natural Resources.

This award reflects Dr. Tablante’s valuable work in extension.

Dr. Osama Mohamed Abas Mohamed Moustafa in Dr. Shi’s lab receives Fulbright Scholar

Ashley Strickland, of Dr. Shi’s Lab, was selected as a recipient for the Jacob K. Goldhaber Travel Grant from The Graduate School of University of Maryland on Feb 10, 2020.

Dr. Mostafa Ghanem’s Lab has acquired a whole-genome sequencer.

This $100,000 equipment is a highthroughput sequencer that could performs up to 25 million reads per run.

Mariam Bakshi joined the Department of Veterinary Medicine as a Post-Doctoral Associate in Dr. Zhu’s Lab. This Photo by Unknown Author is licensed under CC BY-NC

Jack Cook joined the Department of Veterinary Medicine as a Graduate Student in Dr. Riley’s Lab. Jenny Miao joined the Department of Veterinary Medicine as a Graduate Student in Dr. Zhu’s Lab. Bhargave Teja Sallapalli joined the Department of Veterinary Medicine as a Graduate Student in Dr. Zhang’s Lab. Dr. Tao Wang joined the Department of Veterinary Medicine as a Post-Doctoral Associate in Dr. Zhu’s Lab. Dr. Michele Williams joined the Department of Veterinary Medicine as the Associate Lab Director in Dr. Ghanem’s Lab. Cornelia Zhu joined the Department of Veterinary Medicine as a Graduate Student in Dr. Riley’s Lab.

Vet Med Responds to COVID-19 The Coronavirus also known as SARS-CoV-2 had a massive outbreak in 2019 called COVID-19. This ongoing pandemic has changed the lives of many people around the world. Thought to be spread from close personto-person contact, through tiny respiratory droplets in the air, people began to do their part to slow the spread of this highly contagious virus. Individuals started to social distance by eliminating contact, wearing masks, limiting group gatherings, constantly wash their hands and disinfecting surfaces. Schools and businesses, including the University of Maryland, were forced to close allowing workers and students the opportunity to remain at home and practice social distancing. Here in the Department of Veterinary Medicine we continued to perform essential and vital research in response to COVID-19. Dr. George Belov, Dr. Daniel Nelson, Dr. Yanjin Zhang, Dr. Xiaoping Zhu are developing anti-viral therapeutics and vaccines for COVID-19. Additionally, our researchers have submitted proposals for research grants to the Department of Defense, the National Institute of Health and other resources and organizations. We are excited to share some of this research with you in this edition of our newsletter.

SPECIAL COVERAGE: COVID-19 Belov Lab We propose to explore a vector vaccine approach to the development of a safe and affordable vaccine against COVID19. In vector vaccines a protective antigen is expressed from a non-pathogenic viral vector. Such an approach combines safety since the pathogenic organism is not propagated or used at any stage of the vaccine life cycle, with the benefits of live vaccines such as stimulation of the innate immune response since the antigen is expressed in the context of active vector virus replication. Moreover, compared to other common approaches to vaccine development, vectored vaccines are more economically affordable because they rely on propagation of efficiently replicating viral vector. We are using as the vector an avian respiratory virus to express the spike protein of SARS-Cov2 virus. The delivery of such a vector vaccine is not only expected to induce the production of neutralizing antibodies but will also stimulate local immune responses in the respiratory tract, which will provide additional benefits for controlling coronavirus infection. We are testing different designs of the vector vaccine with the modifications of both the vector backbone and the protective antigen to maximize the presentation of the antigen in protective conformation to the immune system.

Nelson Lab

Working with Integrated BioTherapeutics, a private biotechnology company, and researchers at the National Center for Biodefense and Infectious Disease, the Nelson lab in Veterinary Medicine is developing “chimeric� therapeutics for COVID-19 that combine domains of human antibodies with viral-specific binding proteins. The viral-specific binding protein is the ACE2 human receptor that binds the SARS-CoV-2 virus. These chimeras are expected to have several favorable features: i) they are expected to show specific and high affinity to by Unknown Author is licensed under CC BYdirect binding to the SARS-CoV-2 virus via the spike receptor binding domain (RBD); ii) binding is expected to be enhanced by the avidity effect since each chimeric molecule is engineered to be a dimer; iii) most importantly, chimeras are expected to accumulate at the site of infection where virus neutralizing molecules are needed; and iv) chimeras are expected to mediate clearance of SARS-CoV-2 by phagocytes, a very efficient method for viral clearance. Since numerous reports of COVID-19 recurrence are emerging, any existing therapeutic with a half-life below 2 weeks may have limited impact; hence, the approach also proposes to make specific mutations to the antibody domains of the final therapeutic candidates, which has proven to extend the half-life >3 months. Also, we propose constructing chimeras with the goal of further improving safety profiles. Toward this end, therapeutic chimeras will include point mutations to the ACE2 domain known to prevent peptidase activity and/or angiotensin binding while keeping intact the capacity of the chimeras to bind SARS-CoV-2.

Zhang Lab The COVID-19 pandemic has drawn heightened attention due to the troubling impact on public health and the economy across the world. The disease is caused by a new coronavirus, to which no specific antiviral therapeutics or vaccines are available. One of our objectives is to develop specific antiviral compounds that bind to the virus genome and block the proliferation of the coronavirus. The antivirals are expected to have high binding specificity and complete resistance to degradation. Their good target predictability, high efficacy, and bioavailability suggest the prospective clinical application. We will test the antivirals in both cultured cells and mouse models. Another objective is to study the molecular mechanism of the coronavirus infection, specifically virus-cell interactions. We are especially interested in how the virus antagonizes host innate immunity and antiviral cell signaling. Individual viral proteins involved in the interference of host cell signaling will be studied. These studies will provide us with specific antivirals and informative results that may facilitate future development of novel therapeutics against COVID-19.

Zhu Lab The SARS-CoV-2, a highly contagious virus, causes COVID-19 disease with acute lung inflammation, especially in the elderly population; the development of safe and effective vaccines is an urgent need. Since this This Photo by Unknown Author is licensed new virus initiates its infection through the under CC BY-NC respiratory tract, it is important to induce a protective and long-lasting respiratory immunity to block transmission. However, our ability to deliver vaccine antigens across the respiratory epithelial barrier is very limited. The neonatal Fc Receptor (FcRn) mediates the transfer of IgG antibody across respiratory epithelial cells. We have recently found that FcRn can effectively deliver an influenza vaccine antigen in the respiratory tract and elicit potent protection against lethal influenza infection. We hypothesize that FcRn-mediated respiratory immunization can deliver COVID-19 vaccine antigens across the respiratory barrier and induce protective immunity in the lung, consequently blocking virus replication and spread among people. The spike protein of the COVID-19 virus mediates receptor binding and membrane fusion of epithelial cells in the respiratory tract. The spike protein is proposed as a major vaccine antigen because it would induce neutralizing antibodies that prevent host cell attachment and infection by the COVID virus. We have already produced several forms of soluble spike antigens that are targeting to FcRn binding. We will intranasally immunize mice and ferret with these engineered COVID-19 antigens and fully analyze their mucosal, systemic, and memory immune responses, such as neutralizing antibody, mucosal antibody, and memory T cell immune responses in the lung. The vaccine efficacy will be measured by challenging the mice or ferret with COVID-19 virus in ABSL-3+ facility and examine the survival and pathologic changes in the tissues of infected animals.

Grants Dr. Daniel Nelson has received funding to explore the use of viral proteins against the bacteria that cause acne. To read more: click here.

Dr. Utpal Pal and his collaborator Dr. Matthias Schnell at Thomas Jefferson University receives a $3.5 million grant to develop a novel Lyme disease vaccine. To read more: click here.

Dr. Yanjin Zhang has received a seed grant from Indian collaborator to develop a novel therapeutic strategy to treat COVID-19 disease.

Publications Sun D, Sun P, Li H, Zhang M, Liu G, Strickland AB, Chen Y, Fu Y, Xu J, Yosri M, Nan Y, Zhou H, Zhang X, Shi M. Fungal dissemination is limited by liver macrophage filtration of the blood. Nat Commun. 2019 Oct 8;10(1):4566. doi: 10.1038/s41467-019-12381-5.

Liu G, Fu Y, Yosri M, Chen Y, Sun P, Xu J, Zhang M, Sun D, Strickland AB, Mackey ZB, Shi M. CRIg plays an essential role in intravascular clearance of bloodborne parasites by interacting with complement.

Proc Natl Acad Sci U S A. 2019 Nov 26;116(48):24214-24220. doi: 10.1073/pnas.1913443116.

Sun D, Zhang M, Sun P, Liu G, Strickland AB, Chen Y, Fu Y, Yosri M, Shi M. VCAM1/VLA4 interaction mediates Ly6Clow monocyte recruitment to the brain in a TNFR signaling dependent manner during fungal infection. PLoS Pathog. 2020 Feb 26;16(2):e1008361. doi: 10.1371/journal.ppat.1008361. PMID: 32101593; PMCID: PMC7062284.

Sun D, Sun P, He S, Shi M. Rat IgG mediated circulatory cell depletion in mice requires mononuclear phagocyte system and is facilitated by complement. J Leukoc Biol. 2020 Mar;107(3):529-539. doi: 10.1002/JLB.4A1219-078R. Epub 2020 Jan 22. PMID: 31965640.

Li L, Wang H, Zhang J, Sha Y, Wu F, Wen S, He L, Sheng L, You Q, Shi M, Liu L, Zhou H. SPHK1 deficiency protects mice from acetaminophen-induced ER stress and mitochondrial permeability transition. Cell Death Differ. 2020 Jun;27(6):1924-1937. doi: 10.1038/s41418-019-0471-x.

Hu B, Yang M, Liao Z, Wei H, Zhao C, Li D, Hu S, Jiang X, Shi M, Luo Q, Zhang D, Nie Q, Zhang X, Li H. Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken. Front Cell Dev Biol. 2020 Jul 14;8:581. doi: 10.3389/fcell.2020.00581.

Yang L, He J, Wang R, Zhang X, Lin S, Ma Z, Zhang Y. Nonstructural Protein 11 of Porcine Reproductive and Respiratory Syndrome Virus Induces STAT2 Degradation To Inhibit Interferon Signaling. J Virol. 2019 Oct 29;93(22):e01352-19. doi:10.1128/JVI.01352-19.

Lin S, Yang Y, Nan Y, Ma Z, Yang L, Zhang YJ. The Capsid Protein of Hepatitis E Virus Inhibits Interferon Induction via Its N-terminal Arginine-Rich Motif. Viruses. 2019 Nov 11;11(11):1050. doi: 10.3390/v11111050.

Gomes-Solecki M, Arnaboldi PM, Backenson PB, Benach JL, Cooper CL, Dattwyler RJ, Diuk-Wasser M, Fikrig E, Hovius JW, Laegreid W, Lundberg U, Marconi RT, Marques AR, Molloy P, Narasimhan S, Pal U, Pedra JHF, Plotkin S, Rock DL, Rosa P, Telford SR, Tsao J, Yang XF, Schutzer SE. Protective Immunity and New Vaccines for Lyme Disease. Clin Infect Dis. 2020 Apr 10;70(8):1768-1773. doi: 10.1093/cid/ciz872.

Kurokawa C, Lynn GE, Pedra JHF, Pal U, Narasimhan S, Fikrig E. Interactions between Borrelia burgdorferi and ticks. Nat Rev Microbiol. 2020 Jul 10:1-14. doi: 10.1038/s41579-020-0400-5.

Bista S, Singh P, Bernard Q, Yang X, Hart T, Lin YP, Kitsou C, Singh Rana V, Zhang F, Linhardt RJ, Zhang K, Akins DR, Hritzo L, Kim Y, Grab DJ, Dumler JS, Pal U. A Novel Laminin-Binding Protein Mediates Microbial-Endothelial Cell Interactions and Facilitates Dissemination of Lyme Disease Pathogens. J Infect Dis. 2020 Apr 7;221(9):1438-1447. doi: 10.1093/infdis/jiz626.

Marcinkiewicz AL, Lieknina I, Yang X, Lederman PL, Hart TM, Yates J, Chen WH, Bottazzi ME, Mantis NJ, Kraiczy P, Pal U, Tars K, Lin YP. The Factor H-Binding Site of CspZ as a Protective Target against Multistrain, Tick-Transmitted Lyme Disease. Infect Immun. 2020 Apr 20;88(5):e00956-19. doi: 10.1128/IAI.00956-19.

Swift SM, Etobayeva IV, Reid KP, Waters JJ, Oakley BB, Donovan DM, Nelson DC. Characterization of LysBC17, a Lytic Endopeptidase from Bacillus cereus. Antibiotics (Basel). 2019 Sep 19;8(3):155. doi: 10.3390/antibiotics8030155.

Yang H, Luo D, Etobayeva I, Li X, Gong Y, Wang S, Li Q, Xu P, Yin W, He J, Nelson DC, Wei H. Linker Editing of Pneumococcal Lysin ClyJ Conveys Improved Bactericidal Activity. Antimicrob Agents Chemother.

2020 Jan 27;64(2):e01610-19. doi: 10.1128/AAC.01610-19. Print 2020 Jan 27.

Belov GA, van Kuppeveld FJM. Lipid Droplets Grease Enterovirus Replication. Cell Host Microbe. 2019 Aug 14;26(2):149-151. doi: 10.1016/j.chom.2019.07.017.

Viktorova EG, Gabaglio S, Meissner JM, Lee E, Moghimi S, Sztul E, Belov GA. A Redundant Mechanism of Recruitment Underlies the Remarkable Plasticity of the Requirement of Poliovirus Replication for the Cellular ArfGEF GBF1. J Virol. 2019 Oct 15;93(21):e00856-19. doi: 10.1128/JVI.00856-19.

Dimitrov KM, Abolnik C, Afonso CL, Albina E, Bahl J, Berg M, Briand FX, Brown IH, Choi KS, Chvala I, Diel DG, Durr PA, Ferreira HL, Fusaro A, Gil P, Goujgoulova GV, Grund C, Hicks JT, Joannis TM, Torchetti MK, Kolosov S, Lambrecht B, Lewis NS, Liu H, Liu H, McCullough S, Miller PJ, Monne I, Muller CP, Munir M, Reischak D, Sabra M, Samal SK, Servan de Almeida R, Shittu I, Snoeck CJ, Suarez DL, Van Borm S, Wang Z, Wong FYK. Updated unified phylogenetic classification system and revised nomenclature for Newcastle disease virus. Infect Genet Evol. 2019 Oct;74:103917. doi: 10.1016/j.meegid.2019.103917.

Roy Chowdhury I, Yeddula SGR, Pierce BG, Samal SK, Kim SH. Newcastle disease virus vectors expressing consensus sequence of the H7 HA protein protect broiler chickens and turkeys against highly pathogenic H7N8 virus. Vaccine. 2019 Aug 14;37(35):4956-4962. doi: 10.1016/j.vaccine.2019.07.028.

Shirvani E, Samal SK. Newcastle Disease Virus as a Vaccine Vector for SARS-CoV-2. Pathogens. 2020 Jul 29;9(8):E619. doi: 10.3390/pathogens9080619.

Helmy YA, Kathayat D, Ghanem M, Jung K, Closs G Jr, Deblais L, Srivastava V, El-Gazzar M, Rajashekara G. Identification and characterization of novel small molecule inhibitors to control Mycoplasma gallisepticum infection in chickens. Vet Microbiol. 2020 Aug;247:108799. doi: 10.1016/j.vetmic.2020.108799.

Terefe, Y., Deblais, L., Ghanem, M., Helmy, Y. A., Mummed, B., Chen, D., ... & Yousuf Hassen, J. (2020).

Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome. Frontiers in Public Health, 8, 99.

Ghanem, M., & El-Gazzar, M. (2019). Development of a Multilocus Sequence Typing Assay for Mycoplasma gallisepticum. Avian Diseases, 63(4), 693-702.

Liu X, Palaniyandi S, Zhu I, Tang J, Li W, Wu X, Ochsner SP, Pauza CD, Cohen JI, Zhu X. Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor. Nat Commun. 2019 Jul 9;10(1):3020. doi: 10.1038/s41467-019-10865-y.

Palaniyandi S, Rajendrakumar AM, Periasamy S, Goswami R, Tuo W, Zhu X, Rahaman SO. TRPV4 is dispensable for the development of airway allergic asthma. Lab Invest. 2020 Feb;100(2):265-273. doi: 10.1038/s41374-019-0305-y.

Chandrasekaran P, Izadjoo S, Stimely J, Palaniyandi S, Zhu X, Tafuri W, Mosser DM. Regulatory Macrophages Inhibit Alternative Macrophage Activation and Attenuate Pathology Associated with Fibrosis.

J Immunol. 2019 Oct 15;203(8):2130-2140. doi: 10.4049/jimmunol.1900270.

ASSOCIATE DEAN & DEPARTMENT CHAIR Xiaoping Zhu FACULTY

STAFF

George Belov

Yonas Araya

Mostafa Ghanem

Halema Baxter

Weizhong Li

Matthias Corrotte

Daniel Nelson

Aleksandar Dakic

Utpal Pal

Ely Guevara

Sean Riley

Girmay Gebreluul

Siba Samal

Judy Knight

Meiqing Shi

Johanna Lavigne

Nathaniel Tablante

Ricardo Morales

Ekaterina Viktorova

Tam Ong

Xiuli Yang Yanjin Zhang

8075 Greenmead Drive College Park, MD 20742 vetmed.umd.edu Editor: Halema D. Baxter