A10 (20) Part 1 Radiographic and CT Features of Viral Pneumonia

Total Page:16

File Type:pdf, Size:1020Kb

A10 (20) Part 1 Radiographic and CT Features of Viral Pneumonia Radiography Activity for 2020 Activity No: A10 (20) 2023 Topic Viral Pneumonia Article Radiographic and CT Features of Viral Pneumonia Speciality Diagnostic / Medical Technician Part 1 Approved for THREE (3) Clinical Continuing Educational Units (CEU’s) Part 2 Approved for THREE (3) Clinical Continuing Educational Units (CEU’s) This copy is for personal use only. To order printed copies, contact [email protected] 719 CHEST IMAGING Radiographic and CT Features of Viral Pneumonia1 Hyun Jung Koo, MD, PhD Soyeoun Lim, MD Viruses are the most common causes of respiratory infection. The Jooae Choe, MD imaging findings of viral pneumonia are diverse and overlap with Sang-Ho Choi, MD, PhD those of other nonviral infectious and inflammatory conditions. Heungsup Sung, MD However, identification of the underlying viral pathogens may not Kyung-Hyun Do, MD, PhD always be easy. There are a number of indicators for identifying viral pathogens on the basis of imaging patterns, which are associated Abbreviations: CMV = cytomegalovirus, GGO = with the pathogenesis of viral infections. Viruses in the same viral ground-glass opacity, HMPV = human meta- family share a similar pathogenesis of pneumonia, and the imaging pneumovirus, HPIV = human parainfluenza virus, HSV = herpes simplex virus, MERS = patterns have distinguishable characteristics. Although not all cases Middle East respiratory syndrome, RSV = re- manifest with typical patterns, most typical imaging patterns of viral spiratory syncytial virus, SARS = severe acute respiratory syndrome pneumonia can be classified according to viral families. Although a definite diagnosis cannot be achieved on the basis of imaging RadioGraphics 2018; 38:719–739 features alone, recognition of viral pneumonia patterns may aid in https://doi.org/10.1148/rg.2018170048 differentiating viral pathogens, thus reducing the use of antibiotics. Content Codes: Recently, new viruses associated with recent outbreaks including 1From the Department of Radiology and Re- human metapneumovirus, severe acute respiratory syndrome coro- search Institute of Radiology (H.J.K., J.C., navirus, and Middle East respiratory syndrome coronavirus have K.H.D.), Division of Infectious Disease, Depart- ment of Internal Medicine (S.H.C.), and De- been discovered. The imaging findings of these emerging pathogens partment of Laboratory Medicine (H.S.), Asan have been described in a few recent studies. This review focuses Medical Center, University of Ulsan College of on the radiographic and computed tomographic patterns of viral Medicine, Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, South Korea; and Department of Radiol- pneumonia caused by different pathogens, including new patho- ogy, Ulsan University Hospital, Ulsan University gens. Clinical characteristics that could affect imaging, such as College of Medicine, Ulsan, South Korea (S.L.). Presented as an education exhibit at the 2016 patient age and immune status, seasonal variation and community RSNA Annual Meeting. Received March 11, outbreaks, and pathogenesis, are also discussed. The first goal of 2017; revision requested May 18 and received this review is to indicate that there are imaging features that should August 6; accepted August 11. For this journal- based SA-CME activity, the authors, editor, and raise the possibility of viral infections. Second, to help radiologists reviewers have disclosed no relevant relation- differentiate viral infections, viruses in the same viridae that have ships. Address correspondence to K.H.D. (e- mail: [email protected]). similar pathogenesis and can have similar imaging characteristics are shown. By considering both the clinical and radiologic charac- ©RSNA, 2018 teristics, radiologists can suggest the diagnosis of viral pneumonia. SA-CME LEARNING OBJECTIVES ©RSNA, 2018 • radiographics.rsna.org After completing this journal-based SA-CME activity, participants will be able to: ■■Identify radiographic and characteristic CT patterns of viral pneumonia accord- Introduction ing to pathogen. Viruses are the most common causes of acute respiratory infections, ■■Review new viruses including HMPV, and causative agents of lower respiratory tract infection vary accord- SARS coronavirus, MERS coronavirus, ing to patient age and immunity (Table 1). Computed tomographic and H1N1 virus. (CT) findings of viral pneumonia are diverse and may be affected by ■■Discuss the clinical characteristics of the immune status of the host and the underlying pathophysiology viral pneumonia such as patient age and immune status, seasonal variation, and of the viral pathogen. Moreover, coinfection with bacteria is com- community outbreak periods. mon. In a previous study, Pavia (1) suggested that biphasic patterned See www.rsna.org/education/search/RG. illness, consolidation on chest radiographs, and high inflammation markers may increase the likelihood of bacterial coinfection (1). The clinical and CT findings of numerous respiratory viral patho- An earlier incorrect version of gens such as influenza, human parainfluenza virus (HPIV), respira- this article appeared online. tory syncytial virus (RSV), rhinovirus, and adenovirus have been This article was corrected on described (1,2). RSV shows an airway-centric pattern of disease with September 10, 2018. 720 May-June 2018 radiographics.rsna.org ing newly identified viral organisms, and discuss TEACHING POINTS clinical characteristics such as age, immune sta- ■■ Adenovirus pneumonia shows bilateral multifocal GGO with tus, seasonal variation in incidence, and commu- patchy consolidations on CT images and may show lobar or nity outbreak periods of specific infections. segmental distribution indicative of bronchopneumonia that resembles bacterial pneumonia. ■■ At CT, HPIV pneumonia shows multifocal patchy consolida- Pathogenesis of Viral Pneumonia tion with GGO that hinders differentiation of viral from bac- CT patterns of viral pneumonia are related to the terial pneumonia, and approximately one-fourth of patients pathogenesis of pulmonary viral infection (Table show centrilobular nodules with bronchial wall thickening. 2). Although not all cases demonstrate typical ■■ Radiographs in patients with HMPV pneumonia show mul- imaging patterns, most viral pneumonia patterns tilobar infiltrations. CT findings in immunocompetent pa- exhibit similarity on the basis of viridae (Fig 1). tients with HMPV pneumonia have not been described yet; For example, RSV and HPIV replicate in the na- however, bilateral ill-defined centrilobular nodules, branching centrilobular nodules, and GGO are noted in patients with sopharyngeal epithelium, spread to the lungs, and hematologic malignancy. induce bronchiolitis with sloughing of epithelial ■■ Radiographs in patients with influenza pneumonia show bi- cells of the small airways (6). HMPV also infects lateral reticulonodular areas of opacity with or without focal the lung epithelium and induces an inflammatory areas of consolidation, usually in the lower lobes. Poorly de- cascade (7). The CT findings of RSV pneumonia, fined patchy or nodular areas of consolidation that become HPIV pneumonia, and HMPV pneumonia are rapidly confluent and represent either diffuse alveolar damage or superinfection are seen frequently and resolve in 3 weeks. similar. The viruses usually appear as multifocal patchy consolidation with GGO, and centrilobu- ■■ MERS pneumonia appears on CT images as subpleural and basilar airspace lesions, with extensive GGO and consolida- lar nodules with bronchial wall thickening are tion. Cavitation is uncommon. also noticed. Influenza virus diffusely invades the respiratory epithelium, resulting in necrotizing bronchitis and diffuse alveolar damage, which manifest as consolidation (8). Adenovirus affects “tree-in-bud” opacity and bronchial wall thicken- the terminal bronchioles and causes bronchiol- ing. Adenovirus appears as multifocal consolida- itis, which may be accompanied by necrotizing tion or ground-glass opacity (GGO), and GGO bronchopneumonia. Herpes simplex virus (HSV) was more frequently noticed in patients with has cytopathic effects in both the airways and adenovirus pneumonia than in those with other alveoli; these manifest as a multifocal scattered viral infections or bacterial infections. A diffuse airspace pattern of opacity and predominant airspace pattern was seen more frequently in areas of peribronchial consolidation. Intranuclear patients with bacterial infections. On the basis inclusions can be observed in lung biopsy tissue of the imaging patterns of pneumonia, we can or at cytologic examination of bronchoalveolar suggest a differential diagnosis of the pathogen lavage fluid. In a patient with HSV pneumonia during early stages of the infection. Diagnostic who underwent open lung biopsy, areas of GGO tests including radiologic studies and blood or on CT images corresponded to pathologic diffuse serologic tests that could help establish the cause alveolar damage (9). The presence of mono- of pneumonia would reduce the use of antibiot- nuclear or multinuclear epithelial cells containing ics and may improve the clinical course. More- an intranuclear inclusion suggests the diagnosis over, rapid diagnosis can lead to early control of of HSV pneumonia. Similarly, cytomegalovirus potential transmission, thus decreasing overall (CMV) exhibits acute interstitial pneumonia with treatment costs. diffuse alveolar edema with fibrinous exudate. With the recent advancement in molecular Multifocal nodular infiltration represents infected biology and the ability to amplify multiple
Recommended publications
  • Electronic Case Report Form (Ecrf)
    BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Open Supplementary Material 3 Electronic case report form (eCRF) Study: Validation and optimization of the utility of routine data for improving the quality of sepsis management in hospitals (Validierung und Optimierung der Nutzbarkeit von Routinedaten zur Qualitätsverbesserung des Sepsis-Managements im Krankenhaus) Study acronym: OPTIMISE Case-ID: |_________________________________| Explanations: - italic text: Gives explanation, is not presented in the eCRF - blue text: multiple answers possible - italic red text: condition for presentation of item or query rule 1 Schwarzkopf D, et al. BMJ Open 2020; 10:e035763. doi: 10.1136/bmjopen-2019-035763 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Open Supplementary Material 3 A. Identification of patients with sepsis 1000 random cases per study centre need to be documented by trained study physicians 0. Admission and discharge dates a. Where several stays 0 no merged to one case for billing 1 yes reasons? If a = yes, ____ how many stays/cases have Query rule: N >= 2 been merged? b. Admission and discharge Admission date: |__|__|____ Discharge date: |__|__|____ dates Admission date: |__|__|____ Discharge date: |__|__|____ Admission date: |__|__|____ Discharge date: |__|__|____ Admission date: |__|__|____ Discharge date: |__|__|____ Query rule: discharge date after admission date c.
    [Show full text]
  • Complete Sections As Applicable
    This form should be used for all taxonomic proposals. Please complete all those modules that are applicable (and then delete the unwanted sections). For guidance, see the notes written in blue and the separate document “Help with completing a taxonomic proposal” Please try to keep related proposals within a single document; you can copy the modules to create more than one genus within a new family, for example. MODULE 1: TITLE, AUTHORS, etc (to be completed by ICTV Code assigned: 2015.006aM officers) Short title: Implementation of taxon-wide non-Latinized binomial species names in the family Rhabdoviridae (e.g. 6 new species in the genus Zetavirus) Modules attached 1 2 3 4 5 (modules 1 and 10 are required) 6 7 8 9 10 Author(s): ICTV Rhabdoviridae Study Group: Walker, Peter Chair Australia [email protected] Blasdell, Kim Member Australia [email protected] Calisher, Charlie H. Member USA [email protected] Dietzgen, Ralf G. Member Australia [email protected] Kondo, Hideki Member Japan [email protected] Kurath, Gael Member USA [email protected] Longdon, Ben Member UK [email protected] Stone, David Member UK [email protected] Tesh, Robert B. Member USA [email protected] Tordo, Noël Member France [email protected] Vasilakis, Nikos Member USA [email protected] Whitfield, Anna Member USA [email protected] and Kuhn, Jens H., [email protected] Corresponding author with e-mail address: Walker, Peter (ICTV Rhabdoviridae Study Group Chair), [email protected] List the ICTV study group(s) that have seen this proposal: A list of study groups and contacts is provided at http://www.ictvonline.org/subcommittees.asp .
    [Show full text]
  • Commission Directive (Eu)
    L 279/54 EN Offi cial Jour nal of the European Union 31.10.2019 COMMISSION DIRECTIVE (EU) 2019/1833 of 24 October 2019 amending Annexes I, III, V and VI to Directive 2000/54/EC of the European Parliament and of the Council as regards purely technical adjustments THE EUROPEAN COMMISSION, Having regard to the Treaty on the Functioning of the European Union, Having regard to Directive 2000/54/EC of the European Parliament and of the Council of 18 September 2000 on the protection of workers from risks related to exposure to biological agents at work (1), and in particular Article 19 thereof, Whereas: (1) Principle 10 of the European Pillar of Social Rights (2), proclaimed at Gothenburg on 17 November 2017, provides that every worker has the right to a healthy, safe and well-adapted working environment. The workers’ right to a high level of protection of their health and safety at work and to a working environment that is adapted to their professional needs and that enables them to prolong their participation in the labour market includes protection from exposure to biological agents at work. (2) The implementation of the directives related to the health and safety of workers at work, including Directive 2000/54/EC, was the subject of an ex-post evaluation, referred to as a REFIT evaluation. The evaluation looked at the directives’ relevance, at research and at new scientific knowledge in the various fields concerned. The REFIT evaluation, referred to in the Commission Staff Working Document (3), concludes, among other things, that the classified list of biological agents in Annex III to Directive 2000/54/EC needs to be amended in light of scientific and technical progress and that consistency with other relevant directives should be enhanced.
    [Show full text]
  • “The Cellular Context of Rabies Virus Replication – Cell Culture Adaptation, Intra-Neuronal Virus Transport and Development of Host Gene Targeting Vectors”
    “The Cellular Context of Rabies Virus Replication – Cell Culture Adaptation, Intra-Neuronal Virus Transport and Development of Host Gene Targeting Vectors” I n a u g u r a l d i s s e r t a t i o n zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) der Mathematisch-Naturwissenschaftlichen Fakultät der Ernst-Moritz-Arndt-Universität Greifswald vorgelegt von Sabine Nemitz geboren am 14.02.1989 in Rathenow Greifswald, den 20.07.2018 1 Dekan: Prof. Dr. Werner Weitschies 1. Gutachter : PD Dr. Stefan Finke 2. Gutachter: Prof. Dr. Karl-Klaus Conzelmann Tag der Promotion: 05.12.2018 2 3 I. Table of Content I. Table of Content 4 II. List of Abbreviations 7 III. Publications 10 1. SUMMARY 11 2. INTRODUCTION 15 2.1. Classification 16 2.2. Transmission 18 2.3. RABV virion structure and genome organization 19 2.4. RABV proteins 21 2.5. Life cycle 26 2.6. Neuronal transport of RABV particles 28 2.7. Fixed and non-fixed RABV 30 2.8. RABV as vector and research tool 31 2.8.1. Gene regulation via post-transcriptional silencing: RNAi 32 2.8.2. Cytoplasmically replicating RNA viruses as vectors for shRNA synthesis 34 3. AIMS OF THE STUDY 35 4. MATERIAL 36 4.1. Technical equipment 36 4.2. Chemicals 36 4.3. Antibiotics 36 4.4. Standard buffers 37 4.5. Marker 38 4.6. Kits 38 4.7. Cell lines 38 4.8. Cell culture media 39 4.9. Bacteria 41 4.10. Viruses 41 4.11.
    [Show full text]
  • Rhabdoviridae.Pdf
    1 Rhabdoviridae Taxonomy Realm- Ribovira Kingdom- Orthornavirae Phylum- Negarnaviricota Subphylum-Haploviricotina Class- Monjiviricetes Order- Mononegaviriales Family- Rhabdoviridae Genus- Lyssavirus Genus-Ephemerovirus Rhabdoviridae: The family Derivation of names Rhabdoviridae: from rhabdos (Greek) meaning rod, referring to virion morphology. Member taxa Vertebrate host Lyssavirus Novirhabdovirus Perhabdovirus Sprivivirus Tupavirus Vertebrate host, arthropod vector Prepared by Dr. Vandana Gupta Page 1 2 Curiovirus Ephemerovirus Hapavirus Ledantevirus Sripuvirus Tibrovirus Vesiculovirus Invertebrate host Almendravirus Alphanemrhavirus Caligrhavirus Sigmavirus Plant host Cytorhabdovirus Dichorhavirus Nucleorhabdovirus Varicosavirus The family Rhabdoviridae includes 20 genera and 144 species of viruses with negative-sense, single-stranded RNA genomes of approximately 10–16 kb. Virions are typically enveloped with bullet-shaped or bacilliform morphology but non-enveloped filamentous virions have also been reported. The genomes are usually (but not always) single RNA molecules with partially complementary termini. Almost all rhabdovirus genomes have 5 genes encoding the structural proteins (N, P, M, G and L); however, many rhabdovirus genomes encode other proteins in additional genes or in alternative open reading frames (ORFs) within the structural protein genes. The family is ecologically diverse with members infecting plants or animals including mammals, birds, reptiles or fish. Rhabdoviruses are also detected in invertebrates,
    [Show full text]
  • Vol. 23, No. 2, 2019
    The Publication on AIDS Vaccine Research WWW.IAVIREPORT.ORG | VOLUME 23, ISSUE 2 | DECEMBER 2019 A new viral vaccine The history of A new efficacy trial of vector has broad vaccination: adapting the mosaic HIV vaccine potential to the times candidate FROM THE EDITOR “It was the best of times, it was the worst of times…” from Janssen Vaccines & Prevention, part of the Jans- So begins Charles Dickens’s famous historical novel A sen Pharmaceutical Companies of Johnson & Johnson, Tale of Two Cities, published in 1859. Dickens was together with a consortium of public partners, began describing the years leading up to the French their second, and largest, efficacy study (named Revolution, yet it is an oddly apt description of the Mosaico) of Janssen’s mosaic-based HIV vaccine candi- current state of the vaccine field. date (see page 16). This October, the first Ebola vaccine was approved by Based on this, one might think it was the best of times. the European Medicines Agency. This is by all accounts But amidst all this progress, global cases of measles are an important milestone in battling outbreaks of a lethal on the rise, a disease for which a highly effective vaccine infectious disease that most often affects people in devel- has been available for more than 50 years. Last year oping countries. This vaccine, known as Ervebo, was more than 140,000 people worldwide died of measles, rapidly developed in 2014 during the deadliest outbreak most of them children under five years old, and 100 mil- of Ebola in history. It is estimated to be 97.5% effective.
    [Show full text]
  • B Directive 2000/54/Ec of the European
    02000L0054 — EN — 24.06.2020 — 002.001 — 1 This text is meant purely as a documentation tool and has no legal effect. The Union's institutions do not assume any liability for its contents. The authentic versions of the relevant acts, including their preambles, are those published in the Official Journal of the European Union and available in EUR-Lex. Those official texts are directly accessible through the links embedded in this document ►B DIRECTIVE 2000/54/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 18 September 2000 on the protection of workers from risks related to exposure to biological agents at work (seventh individual directive within the meaning of Article 16(1) of Directive 89/391/EEC) (OJ L 262, 17.10.2000, p. 21) Amended by: Official Journal No page date ►M1 Commission Directive (EU) 2019/1833 of 24 October 2019 L 279 54 31.10.2019 ►M2 Commission Directive (EU) 2020/739 of 3 June 2020 L 175 11 4.6.2020 02000L0054 — EN — 24.06.2020 — 002.001 — 2 ▼B DIRECTIVE 2000/54/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 18 September 2000 on the protection of workers from risks related to exposure to biological agents at work (seventh individual directive within the meaning of Article 16(1) of Directive 89/391/EEC) CHAPTER I GENERAL PROVISIONS Article 1 Objective 1. This Directive has as its aim the protection of workers against risks to their health and safety, including the prevention of such risks, arising or likely to arise from exposure to biological agents at work.
    [Show full text]
  • Taxonomy of the Order Mononegavirales: Update 2019
    Archives of Virology (2019) 164:1967–1980 https://doi.org/10.1007/s00705-019-04247-4 VIROLOGY DIVISION NEWS Taxonomy of the order Mononegavirales: update 2019 Gaya K. Amarasinghe1 · María A. Ayllón2,3 · Yīmíng Bào4 · Christopher F. Basler5 · Sina Bavari6 · Kim R. Blasdell7 · Thomas Briese8 · Paul A. Brown9 · Alexander Bukreyev10 · Anne Balkema‑Buschmann11 · Ursula J. Buchholz12 · Camila Chabi‑Jesus13 · Kartik Chandran14 · Chiara Chiapponi15 · Ian Crozier16 · Rik L. de Swart17 · Ralf G. Dietzgen18 · Olga Dolnik19 · Jan F. Drexler20 · Ralf Dürrwald21 · William G. Dundon22 · W. Paul Duprex23 · John M. Dye6 · Andrew J. Easton24 · Anthony R. Fooks25 · Pierre B. H. Formenty26 · Ron A. M. Fouchier17 · Juliana Freitas‑Astúa27 · Anthony Grifths28 · Roger Hewson29 · Masayuki Horie31 · Timothy H. Hyndman32 · Dàohóng Jiāng33 · Elliott W. Kitajima34 · Gary P. Kobinger35 · Hideki Kondō36 · Gael Kurath37 · Ivan V. Kuzmin38 · Robert A. Lamb39,40 · Antonio Lavazza15 · Benhur Lee41 · Davide Lelli15 · Eric M. Leroy42 · Jiànróng Lǐ43 · Piet Maes44 · Shin‑Yi L. Marzano45 · Ana Moreno15 · Elke Mühlberger28 · Sergey V. Netesov46 · Norbert Nowotny47,48 · Are Nylund49 · Arnfnn L. Økland49 · Gustavo Palacios6 · Bernadett Pályi50 · Janusz T. Pawęska51 · Susan L. Payne52 · Alice Prosperi15 · Pedro Luis Ramos‑González13 · Bertus K. Rima53 · Paul Rota54 · Dennis Rubbenstroth55 · Mǎng Shī30 · Peter Simmonds56 · Sophie J. Smither57 · Enrica Sozzi15 · Kirsten Spann58 · Mark D. Stenglein59 · David M. Stone60 · Ayato Takada61 · Robert B. Tesh10 · Keizō Tomonaga62 · Noël Tordo63,64 · Jonathan S. Towner65 · Bernadette van den Hoogen17 · Nikos Vasilakis10 · Victoria Wahl66 · Peter J. Walker67 · Lin‑Fa Wang68 · Anna E. Whitfeld69 · John V. Williams23 · F. Murilo Zerbini70 · Tāo Zhāng4 · Yong‑Zhen Zhang71,72 · Jens H. Kuhn73 Published online: 14 May 2019 © This is a U.S.
    [Show full text]
  • Nanopore Assay Reveals Cell-Type-Dependent Gene Expression of Indiana Vesiculovirus and Differential Host Cell Response
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 9 August 2021 doi:10.20944/preprints202108.0195.v1 Nanopore Assay Reveals Cell-type-dependent Gene Expression of Indiana Vesiculovirus and Differential Host Cell Response Balázs Kakuk1#, András A. Kiss1#, Gábor Torma1, Zsolt Csabai1, István Prazsák, Máté Mizik, Klára Megyeri2, Dóra Tombácz1, Zsolt Boldogkői1* 1 Department of Medical Biology, Faculty of Medicine, University of Szeged, Szeged, Hungary 2 Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary. * Corresponding author: Zsolt Boldogkői ([email protected]) # These three authors contributed equally to this work BK: [email protected] GT: [email protected] AK: [email protected] ZC: [email protected] IP: [email protected] MM: [email protected] KM: [email protected] DT: [email protected] ZB: [email protected] keywords: vesicular stomatitis virus, IVV, transcriptome, nanopore sequencing, long-read sequencing Abstract Indiana Vesiculovirus (IVV; formerly as Vesicular stomatitis virus and Vesicular stomatitis Indiana virus) causes a disease in livestock that is very similar to the foot and mouth disease thereby an outbreak may lead to significant economic loss. Long-read sequencing (LRS) -based approaches revealed a hidden complexity of the transcriptomes in several viruses already. This technique was utilized already for the sequencing of the IVV genome, but our study is the first for the application of this technique for the profiling of IVV transcriptome. Since LRS is able to sequence full-length RNA molecules, and thereby providing more accurate annotation of the transcriptomes than the traditional short-read sequencing methods.
    [Show full text]
  • Structures of the Mononegavirales Polymerases
    MINIREVIEW crossm Structures of the Mononegavirales Polymerases Bo Lianga aDepartment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA ABSTRACT Mononegavirales, known as nonsegmented negative-sense (NNS) RNA vi- Downloaded from ruses, are a class of pathogenic and sometimes deadly viruses that include rabies virus (RABV), human respiratory syncytial virus (HRSV), and Ebola virus (EBOV). Unfortunately, no effective vaccines and antiviral therapeutics against many Mononegavirales are cur- rently available. Viral polymerases have been attractive and major antiviral therapeutic targets. Therefore, Mononegavirales polymerases have been extensively investigated for their structures and functions. Mononegavirales mimic RNA synthesis of their eukaryotic counterparts by utilizing multifunctional RNA polymerases to replicate entire viral ge- nomes and transcribe viral mRNAs from individual viral genes as well as synthesize http://jvi.asm.org/ 5= methylated cap and 3= poly(A) tail of the transcribed viral mRNAs. The catalytic subunit large protein (L) and cofactor phosphoprotein (P) constitute the Mononega- virales polymerases. In this review, we discuss the shared and unique features of RNA synthesis, the monomeric multifunctional enzyme L, and the oligomeric multi- modular adapter P of Mononegavirales. We outline the structural analyses of the Mononegavirales polymerases since the first structure of the vesicular stomatitis virus (VSV) L protein determined in 2015 and highlight multiple high-resolution cryo- on October 27, 2020 by guest electron microscopy (cryo-EM) structures of the polymerases of Mononegavirales, namely, VSV, RABV, HRSV, human metapneumovirus (HMPV), and human parainflu- enza virus (HPIV), that have been reported in recent months (2019 to 2020). We compare the structures of those polymerases grouped by virus family, illustrate the similarities and differences among those polymerases, and reveal the potential RNA synthesis mechanisms and models of highly conserved Mononegavirales.
    [Show full text]
  • A Prenylated Dsrna Sensor Protects Against Severe COVID-19 and Is Absent in Horseshoe Bats
    medRxiv preprint doi: https://doi.org/10.1101/2021.05.05.21256681; this version posted May 9, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . @WilsonlabCVR Wickenhagen et al., A Prenylated dsRNA Sensor Protects Against Severe COVID-19 and is ABsent in Horseshoe Bats A Prenylated dsRNA Sensor Protects on global health, culture and prosperity. SARS-CoV-2 is Against Severe COVID-19 and is Absent in particularly sensitive to inhibition by type I interferons (IFNs) and there is great interest in understanding how individual Horseshoe Bats IFN-stimulated genes (ISGs) inhibit SARS-CoV-2, as type I IFNs play a major role in governing COVID-19 disease Arthur Wickenhagen1, Elena Sugrue1*, Spyros Lytras1*, 1* 1 1 outcome. Specifically, inborn errors (Zhang et al., 2020) Srikeerthana Kuchi , Matthew L Turnbull , Colin Loney , and single nucleotide polymorphisms (Pairo-Castineira et 1 1 1 Vanessa Herder , Jay Allan , Innes Jarmson , Natalia al., 2020) within the IFN system are linked with more severe 1 1 1 Cameron-Ruiz , Margus Varjak , Rute M Pinto , Douglas G COVID-19. Moreover, neutralizing anti-IFN autoantibodies 1 1 1 Stewart , Simon Swingler , Marko Noerenberg , Edward J likely prevent host IFN responses from controlling SARS- 2 2 1 D Greenwood , Thomas W M Crozier , Quan Gu , Sara CoV-2 replication, again resulting in severe COVID-19 3 3 4 Clohisey , Bo Wang , Fabio Trindade Maranhão Costa , disease (Bastard et al., 2020).
    [Show full text]
  • Visualization of Protein Sequence Space with Force-Directed Graphs, and Their Application to the Choice of Target-Template Pairs for Homology Modelling
    Accepted Manuscript Visualization of protein sequence space with force-directed graphs, and their application to the choice of target-template pairs for homology modelling Dylan J.T. Mead, Simón Lunagomez, Derek Gatherer PII: S1093-3263(19)30333-X DOI: https://doi.org/10.1016/j.jmgm.2019.07.014 Reference: JMG 7417 To appear in: Journal of Molecular Graphics and Modelling Received Date: 7 May 2019 Revised Date: 23 July 2019 Accepted Date: 25 July 2019 Please cite this article as: D.J.T. Mead, Simó. Lunagomez, D. Gatherer, Visualization of protein sequence space with force-directed graphs, and their application to the choice of target-template pairs for homology modelling, Journal of Molecular Graphics and Modelling (2019), doi: https:// doi.org/10.1016/j.jmgm.2019.07.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT MANUSCRIPT ACCEPTED Force-directed graphs, homology modelling and the structure–sequence gap ACCEPTED MANUSCRIPT TITLE PAGE Visualization of protein sequence space with force- directed graphs, and their application to the choice of target-template pairs for homology modelling. Dylan J.T. Mead 1, Simón Lunagomez 2 & Derek Gatherer 1* (surnames underlined) 1 Division of Biomedical & Life Sciences, Faculty of Health & Medicine, Lancaster University, Lancaster LA1 4YT, UK.
    [Show full text]