Identification of a Ruminant Origin Group B Rotavirus Associated With
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Reverse Genetic Strategies to Interrogate Reassortment Restriction Among Group a Rotaviruses
REVERSE GENETIC STRATEGIES TO INTERROGATE REASSORTMENT RESTRICTION AMONG GROUP A ROTAVIRUSES BY JESSICA R. HALL A Thesis Submitted to the Graduate FACulty of WAKE FOREST UNIVERSITY GRADUATE SCHOOL OF ARTS AND SCIENCES in PArtiAl Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE Biology August 2019 Winston-SAlem, North Carolina Approved By: SArah M. MCDonald, Ph.D., Advisor GloriA K. Muday, Ph.D., Chair DouglAs S. Lyles, Ph.D. JAmes B. PeAse, Ph.D. ACKNOWLEDGEMENTS This body of work wAs mAde possible by the influences of Countless people including, but not limited to, those named here. First, I Am thankful for my Advisor, Dr. SArah MCDonald, who paved wAy for this opportunity. Her infeCtious enthusiAsm for sCience served As A Consistent reminder to “keep getting baCk on the horse”. I Am grateful for my Committee members, Drs. DouglAs Lyles, GloriA Muday, And JAmes PeAse whose input And AdviCe Aided in my development into A CAreful sCientist who thinks CritiCAlly About her work. I Am Also thankful for Continued mentorship from my undergraduate reseArch advisor, Dr. NAthan Coussens, whose enthusiAsm for sCience inspired mine. I Am AppreCiAtive of All of my friends for their unyielding support. I Am blessed to have A solid foundation in my FAmily, both blood And Chosen. I Am thankful for my mother, LiAna HAll, who instilled in me my work ethiC And whose pride in me has inspired me to keep pursuing my dreAms. I Am forever indebted to Dr. DiAna Arnett, who has served As my personal And sCientifiC role model; thank you for believing in me, investing in me, And shaping me into the person and sCientist I am today. -
10.2.2 Nomenclature of Viruses and Taxonomic Groups Bacterial Viruses Such As T1, T2 and Φx174
Classification and nomenclature of viruses History of virus classification • Type of host • Type of disease • Transmition by an arthropod vector • Nucleic acid type • SS or DS • Segmented • Size of the virion • Capsid simmetry • Envelope Nomenclature • Small, icosahedral, single-stranded DNA viruses of animals were called parvoviruses (Latin parvus = small) • Nematode-transmitted polyhedral (icosahedral) viruses of plants were called nepoviruses • Phages T2, T4 and T6 were called T even phages • Serological relationships between viruses were investigated • Distinct strains (serotypes) could be distinguished in serological tests • Antisera against purified virions • Serotypes reflect differences in virus proteins International Committee on Taxonomy of Viruses • Order had to be brought • ICTV was formed in 1966 • Many working groups and is advised by virologists around the world • Rules for the nomenclature and classification of viruses • Considers proposals for new taxonomic groups and virus names • Approved are published in book form and on the web Modern virus classification and nomenclature • Each order, family, subfamily and genus is defined by viral characteristics that are necessary for membership of that group. Classification based on genome sequences • Similarity is represented in diagrams known as phylogenetic trees. • Rooted- the tree begins at a root which is assumed to be the ancestor of the viruses in the tree. • Unrooted- no assumption is made about the ancestor of the viruses in the tree. 10.2.2 Nomenclature of viruses and taxonomic groups Bacterial viruses such as T1, T2 and ϕX174. Viruses of humans and other vertebrates diseases that they cause Examples: measles virus, smallpox virus, foot and mouth disease virus Some viruses city, town or river Examples: Newcastle disease virus, Norwalk virus, Ebola virus Insect viruses Many insect viruses were named after the insect, with an indication of the effect of infection on the host. -
Lessons Learned from Ebola Virus
membranes Review SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus Jordana Muñoz-Basagoiti 1,†, Daniel Perez-Zsolt 1,†, Jorge Carrillo 1 , Julià Blanco 1,2 , Bonaventura Clotet 1,2,3 and Nuria Izquierdo-Useros 1,* 1 IrsiCaixa AIDS Research Institute, Germans Trias I Pujol Research Institute (IGTP), Can Ruti Campus, 08916 Badalona, Spain; [email protected] (J.M.-B.); [email protected] (D.P.-Z.); [email protected] (J.C.); [email protected] (J.B.); [email protected] (B.C.) 2 Infectious Diseases and Immunity Department, Faculty of Medicine, University of Vic (UVic-UCC), 08500 Vic, Spain 3 Infectious Diseases Department, Germans Trias i Pujol Hospital, 08916 Badalona, Spain * Correspondence: [email protected] † These authors contribution is equally to this work. Abstract: Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS- CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, Citation: Muñoz-Basagoiti, J.; antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against Perez-Zsolt, D.; Carrillo, J.; Blanco, J.; the new coronavirus. -
A SARS-Cov-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing Supplementary Information Supplementary Discussion All SARS-CoV-2 protein and gene functions described in the subnetwork appendices, including the text below and the text found in the individual bait subnetworks, are based on the functions of homologous genes from other coronavirus species. These are mainly from SARS-CoV and MERS-CoV, but when available and applicable other related viruses were used to provide insight into function. The SARS-CoV-2 proteins and genes listed here were designed and researched based on the gene alignments provided by Chan et. al. 1 2020 . Though we are reasonably sure the genes here are well annotated, we want to note that not every protein has been verified to be expressed or functional during SARS-CoV-2 infections, either in vitro or in vivo. In an effort to be as comprehensive and transparent as possible, we are reporting the sub-networks of these functionally unverified proteins along with the other SARS-CoV-2 proteins. In such cases, we have made notes within the text below, and on the corresponding subnetwork figures, and would advise that more caution be taken when examining these proteins and their molecular interactions. Due to practical limits in our sample preparation and data collection process, we were unable to generate data for proteins corresponding to Nsp3, Orf7b, and Nsp16. Therefore these three genes have been left out of the following literature review of the SARS-CoV-2 proteins and the protein-protein interactions (PPIs) identified in this study. -
Thiopurines Activate an Antiviral Unfolded Protein Response That
bioRxiv preprint doi: https://doi.org/10.1101/2020.09.30.319863; this version posted October 1, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Thiopurines activate an antiviral unfolded protein response that blocks viral glycoprotein 2 accumulation in cell culture infection model 3 Patrick Slaine1, Mariel Kleer 2, Brett Duguay 1, Eric S. Pringle 1, Eileigh Kadijk 1, Shan Ying 1, 4 Aruna D. Balgi 3, Michel Roberge 3, Craig McCormick 1, #, Denys A. Khaperskyy 1, # 5 6 1Department of Microbiology & Immunology, Dalhousie University, 5850 College Street, Halifax 7 NS, Canada B3H 4R2 8 2Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, 3330 9 Hospital Drive NW, Calgary AB, Canada T2N 4N1 10 3Department of Biochemistry and Molecular Biology, 2350 Health Sciences Mall, University of 11 British Columbia, Vancouver BC, Canada V6T 1Z3 12 13 14 #Co-corresponding authors: C.M., [email protected], D.A.K., [email protected] 15 16 17 Running Title: Drug-induced antiviral unfolded protein response 18 Keywords: virus, influenza, coronavirus, SARS-CoV-2, thiopurine, 6-thioguanine, 6- 19 thioguanosine, unfolded protein response, hemagglutinin, neuraminidase, glycosylation, host- 20 targeted antiviral 21 22 23 ABSTRACT 24 Enveloped viruses, including influenza A viruses (IAVs) and coronaviruses (CoVs), utilize the 25 host cell secretory pathway to synthesize viral glycoproteins and direct them to sites of assembly. 26 Using an image-based high-content screen, we identified two thiopurines, 6-thioguanine (6-TG) 27 and 6-thioguanosine (6-TGo), that selectively disrupted the processing and accumulation of IAV 28 glycoproteins hemagglutinin (HA) and neuraminidase (NA). -
WHO Immunological Basis for Immunization Series
WHO Immunological Basis for Immunization Series Module 21: Rotavirus Update 2019 Department of Immunization, Vaccines and Biologicals World Health Organization 20, Avenue Appia CH-1211 Geneva 27, Switzerland [email protected] http://www.who.int/immunization/en/ Immunization, Vaccines and Biologicals WHO Immunological Basis for Immunization Series Module 21: Rotavirus Update 2019 Immunization, Vaccines and Biologicals The immunological basis for immunization series: module 21: Rotavirus Vaccines (Immunological basis for immunization series; module 21) ISBN 978-92-4-000235-7 © World Health Organization 2020 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. -
NSP4)-Induced Intrinsic Apoptosis
viruses Article Viperin, an IFN-Stimulated Protein, Delays Rotavirus Release by Inhibiting Non-Structural Protein 4 (NSP4)-Induced Intrinsic Apoptosis Rakesh Sarkar †, Satabdi Nandi †, Mahadeb Lo, Animesh Gope and Mamta Chawla-Sarkar * Division of Virology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road Scheme-XM, Beliaghata, Kolkata 700010, India; [email protected] (R.S.); [email protected] (S.N.); [email protected] (M.L.); [email protected] (A.G.) * Correspondence: [email protected]; Tel.: +91-33-2353-7470; Fax: +91-33-2370-5066 † These authors contributed equally to this work. Abstract: Viral infections lead to expeditious activation of the host’s innate immune responses, most importantly the interferon (IFN) response, which manifests a network of interferon-stimulated genes (ISGs) that constrain escalating virus replication by fashioning an ill-disposed environment. Interestingly, most viruses, including rotavirus, have evolved numerous strategies to evade or subvert host immune responses to establish successful infection. Several studies have documented the induction of ISGs during rotavirus infection. In this study, we evaluated the induction and antiviral potential of viperin, an ISG, during rotavirus infection. We observed that rotavirus infection, in a stain independent manner, resulted in progressive upregulation of viperin at increasing time points post-infection. Knockdown of viperin had no significant consequence on the production of total Citation: Sarkar, R.; Nandi, S.; Lo, infectious virus particles. Interestingly, substantial escalation in progeny virus release was observed M.; Gope, A.; Chawla-Sarkar, M. upon viperin knockdown, suggesting the antagonistic role of viperin in rotavirus release. Subsequent Viperin, an IFN-Stimulated Protein, studies unveiled that RV-NSP4 triggered relocalization of viperin from the ER, the normal residence Delays Rotavirus Release by Inhibiting of viperin, to mitochondria during infection. -
Functional Studies of the Coronavirus Nonstructural Proteins Yanglin QIU and Kai XU*
REVIEW ARTICLE Functional studies of the coronavirus nonstructural proteins Yanglin QIU and Kai XU* Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing 210023, P. R. China. *Correspondence: [email protected] https://doi.org/10.37175/stemedicine.v1i2.39 ABSTRACT Coronaviruses, including SARS-CoV, SARS-CoV-2, and MERS-CoV, have caused contagious and fatal respiratory diseases in humans worldwide. Notably, the coronavirus disease 19 (COVID-19) caused by SARS-CoV-2 spread rapidly in early 2020 and became a global pandemic. The nonstructural proteins of coronaviruses are critical components of the viral replication machinery. They function in viral RNA transcription and replication, as well as counteracting the host innate immunity. Studies of these proteins not only revealed their essential role during viral infection but also help the design of novel drugs targeting the viral replication and immune evasion machinery. In this review, we summarize the functional studies of each nonstructural proteins and compare the similarities and differences between nonstructural proteins from different coronaviruses. Keywords: Coronavirus · SARS-CoV-2 · COVID-19 · Nonstructural proteins · Drug discovery Introduction genes (18). The first two major ORFs (ORF1a, ORF1ab) The coronavirus (CoV) outbreaks among human are the replicase genes, and the other four encode viral populations have caused three major epidemics structural proteins that comprise the essential protein worldwide, since the beginning of the 21st century. These components of the coronavirus virions, including the spike are the epidemics of the severe acute respiratory syndrome surface glycoprotein (S), envelope protein (E), matrix (SARS) in 2003 (1, 2), the Middle East respiratory protein (M), and nucleocapsid protein (N) (14, 19, 20). -
Rotavirus Fact Sheet
ROTAVIRUS FACT SHEET What is Rotavirus? commonly spreads in families, hospitals, and childcare Rotavirus is a virus that commonly causes inflammation centers. A person with rotavirus disease is most likely to of the stomach and intestines (acute gastroenteritis). spread the virus from the time they are sick through the first 3 days after they recover. Who can get Rotavirus disease? Anyone. However, it is most common in infants and Is there a vaccine for Rotavirus? young children. A person may be infected more than Yes. The vaccine is highly effective at preventing severe once. Nearly every child who is not vaccinated as an rotavirus disease in infants and young children. The infant is expected to be infected within the first years of vaccine is given orally starting at age 2 months as a life. series of 2 doses or 3 doses, depending on the specific type. What are the symptoms of Rotavirus disease? Children with rotavirus disease may have severe watery How can the spread of Rotavirus be prevented? diarrhea, vomiting, fever, abdominal pain, and loss of The virus spreads so easily that frequent handwashing appetite. Vomiting and diarrhea can lead to dehydration. with soap and water is important, but not sufficient for Signs of dehydration include decreased urination, dry controlling the spread of the disease. Rotavirus mouth and throat, and feeling dizzy when standing up. A vaccination is the best way to protect children against child who is dehydrated may have few or no tears when rotavirus disease. crying and be unusually sleepy or fussy. Usually a person’s first infection with rotavirus tends to cause the How is Rotavirus disease treated? most severe symptoms. -
Pink Book Webinar Series: Rotavirus and Hepatitis a Slides
Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Rotavirus and Hepatitis A Pink Book Webinar Series 2018 Mark Freedman, DVM, MPH Veterinary Medical Officer Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Rotavirus: Disease and Vaccine Rotavirus . First identified as a cause of diarrhea in 1973 . Most common cause of severe gastroenteritis in infants and young children . Nearly universal infection by age 5 years . Responsible for up to 500,000 diarrheal deaths each year worldwide Rotavirus . Two important outer shell proteins—VP7, or G-protein, and VP4, or P-protein define the serotype of the virus . From 1996–2005, five predominate strains in the U.S. (G1–G4, G9) accounted for 90% of the isolates . G1 strain accounts for 75% of infections . Very stable and may remain viable for weeks or months if not disinfected Rotavirus Immunity . Antibody against VP7 and VP4 probably important for protection • Cell-mediated immunity probably plays a role in recovery and immunity . First infection usually does not lead to permanent immunity . Reinfection can occur at any age . Subsequent infections generally less severe Rotavirus Clinical Features . Short incubation period . First infection after 3 months of age generally most severe . May be asymptomatic or result in severe, dehydrating diarrhea with fever and vomiting . Gastrointestinal symptoms generally resolve in 3–7 days Rotavirus Complications . Infection can lead to severe diarrhea, dehydration, electrolyte imbalance, and metabolic acidosis . -
Detailed Review Paper on Rotavirus Vaccines
Rotavirus Vaccines 17 March 2009 Detailed Review Paper on Rotavirus Vaccines To be presented to the WHO Strategic Advisory Group of Experts (SAGE) on Immunization, April 2009 Ad-hoc group of experts on rotavirus vaccines Chair : G. Peter Members: T. Aguado, Z. Bhutta, L. De Oliveira, K. Neuzil, U. Parashar, D. Steele WHO Secretariat: C. Mantel, S. Wang, G. Mayers, E. Derobert Rapporteur: D. Payne 1 Rotavirus Vaccines 17 March 2009 Table of Contents I. Rotavirus Epidemiology and Rationale for Vaccination 1. Disease burden 2. Rationale for vaccination as the primary preventive measure II. Rotavirus Vaccine Efficacy and Safety in Pivotal Pre-Licensure Trials Brief summary of rotavirus vaccines 1. Rotarix ® 2. RotaTeq ® III. Newly Available Data from Clinical Trials in Africa and Asia and Post-introduction Vaccine Effectiveness Evaluations in the Americas 1. South Africa and Malawi clinical trials (Rotarix ®) 2. Hong Kong, Taiwan, and Singapore clinical trials (Rotarix ®) 3. Nicaragua post-introduction vaccine effectiveness case- control study (RotaTeq ®) 4. El Salvador post-introduction vaccine effectiveness case- control study (Rotarix ®) 5. United States post-licensure impact evaluation studies 6. Status of other ongoing studies IV. Vaccine Safety, Co-Administration, and Special Populations 1. Vaccine safety 2. Co-administration with other vaccines, particularly OPV 3. HIV-infected populations 4. Breast-feeding and Pre-term Infants V. Vaccine Schedules and Age Restrictions VI. Vaccine Cost-effectiveness and Decision-Making Regarding Program Implementation 1. Cost-effectiveness and affordability 2. Decision-making regarding vaccine introduction VII. Vaccine Program Implementation and Vaccine Delivery Logistics VIII. Integration with Diarrheal Control and Other Health Interventions and Communication 1. -
RIDA®QUICK Rota/Adeno/Noro Combi Quick Detection of the Three Main Viral Gastroenteritis Agents
R-Biopharm – dedicated to food safety RIDA®QUICK Rota/Adeno/Noro Combi Quick detection of the three main viral gastroenteritis agents • Distinction between Noroviruses of genogroup I and genogroup II • Quick detection of outbreaks and mixed infections • Kit includes ready-to-use stool extraction vials • Simple test execution R-Biopharm – dedicated to food safety The three main viral gastroenteritis agents Despite the introduction of a vaccine, rotavirus is associated gastroenteritis and the third most still the most common cause of severe diarrhea common causal agent of viral gastroenteritis in in children under the age of five. In high-risk children. groups (children, immunosuppressed and elderly One in five cases of acute gastroenteritis worldwide patients) severe forms of disease can occur, making is caused by the norovirus. In developing countries, rotaviruses particularly significant in nosocomial norovirus causes the death of an estimated 50,000 infections in nursery and pediatric wards and children. Norovirus incurs a cost of 60 billion USD intensive care and oncology units. In 2013, an every year in medical care and productivity losses. estimated 215,000 children worldwide died from a rotavirus infection. The use of the RIDA®QUICK Rota/Adeno/Noro Combi, available as a double cassette, allows for Adenoviruses can cause infections of the eyes, quick and sensitive detection of the most significant respiratory or gastrointestinal tract. Types 40/41 of viral gastroenteritis agents. the adenovirus are the major cause of adenovirus- Perspective – Mixed infections In practice, mixed infections involving two or more gastroenteritis agents are often observed. RIDA®QUICK Rota/Adeno/Noro Combi enables rapid detection of single and mixed infections within 15 minutes.