Coronaviruses - Coronaviridae

1. Coronaviruses - Coronaviridae Virion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics

2. Coronaviruses - Coronaviridae • Virion • Spherical enveloped particles studded with clubbed spikes. • Diameter 120–160 nm. • Coiled helical nucleocapsid. • Core shell may be icosahedral.

3. Coronaviruses - Coronaviridae • Genome • Linear ss RNA, positive sense. • 27–32 Kb. • 5 terminal cap. • 3 poly(A) tail.

4. Coronaviruses - Coronaviridae • Genes and proteins • Six–nine genes code for more than twenty proteins. • Replicase genes translated directly from genome RNA: • Two large open reading frames joined by frameshift • Translated as polyprotein, cleaved to fourteen–sixteen proteins • Other genes translated from multiple 3-coterminal, subgenomic mRNAs: • Three–four envelope proteins (HE, S, E, M) • One nucleocapsid protein (N) • Four–six nonstructural or accessory proteins

5. Coronaviruses - Coronaviridae • Viruses and hosts • Three subgroups based on antigenic and genome homologies. • Humans: human coronaviruses 229E, OC43, NL63, HKU-1; SARS coronavirus. • Animals including mice, dogs, cats, pigs, cattle, turkeys, bats: murine hepatitis virus (MHV), transmissible gastroenteritis virus • (TGEV), avian infectious bronchitis virus (IBV).

6. Coronaviruses - Coronaviridae • Diseases • Responsible for up to 30% of common colds in humans. • Severe acute respiratory syndrome (SARS): pneumonia in humans with 10% fatality rate. • Important veterinary diseases: severe endemic and epidemic respiratory, hepatic, gastrointestinal, and neurological diseases in • mammalian and avian species. • Virus spreads between hosts by direct contact, aerosol and fecal-oral transmission, and contact with contaminated surfaces.

7. Coronaviruses - Coronaviridae • Distinctive characteristics • Largest known RNA virus genome. • Large replicase polyprotein cleaved by viral proteinases to numerous functional proteins.

8. Virion • Coronaviruses cause common colds in humans and important veterinary diseases • A newly emerged coronavirus caused a worldwide epidemic of severe acute respiratory syndrome (SARS) • The SARS coronavirus may have passed from animals to humans via direct contact • Chinese horseshoe bat is natural host

9. Genome • Coronaviruses have large, single-stranded, positive-sense RNA genomes Fig. 19.1 Coronaviruses have large, single-stranded, positive-sense RNA genomes

10. Genome • Coronaviruses fall into three groups based on genome sequences

11. Virion • Coronaviruses have enveloped virions containing helical nucleocapsids Fig. 19.2 Coronavirus virion.

12. Genome • Coronavirus virions contain multiple envelope proteins • Spike protein (S) • Responsible for virus entry and spread • Determine host range • Target for neutralizing Ab and CTL response • Hemagglutinin-esterase protein (HE) • Found in group II • Not essential structural protein • Functionally similar to influenza HA, NA • May play a role in binding and entry of coronavirus • May facilitate virus release from cell surface

13. Genome • Coronavirus virions contain multiple envelope proteins • Membrane protein (M) • Highly conserved • Play a role in virus assembly • Small envelope protein (E) • Facilitate budding into lumen of ER and Golgi • Mutant lacking E is viable

14. Genome • Coronavirus spike proteins bind to a variety of cellular receptors • Group 1 : Aminopeptidase-N • Group 2 : CEACAM1 • SARS : ACE2 • HE- sialic acid • The virus envelope fuses with the plasma membrane or an endosomal membrane • S mediates fusion of viral envelope and cellular membrane • S can also induce cell-cell fusion

15. Genes and proteins • The replicase gene is translated from genome RNA into a polyprotein that is processed by viral proteinases • Gene 1 • Comprise the 5’ two-thirds of the RNA genome • Organized as two partially overlapping ORFs • ORF1a, ORF1b • May control the levels of proteins of ORF1a and ORF1b

16. Genes and proteins • RNA polymerase, RNA helicase, and RNA modifying enzymes are coded by the replicase gene • Table 19.2

17. Genes and proteins

18. Genes and proteins • Replication complexes are associated with cytoplasmic membranes • Membrane association of viral RNA synthesis is common pattern among eukaryotic positive-strand RNA viruses • Genome replication proceeds via a full length negative-strand intermediate

19. Genes and proteins • Transcription produces a nested set of subgenomic mRNAs Fig. 19.3 Coronavirus messenger RNAs: a nested set.

20. Genes and proteins • Subgenomic mRNAs are most likely transcribed from subgenomic negative-sense RNA templates Fig. 19.4 Discontinuous transcription of genome RNA: a model for coronavirus mRNA production.

21. Genes and proteins • Assembly of virions takes place at intracellular membrane structures Fig. 19.5 Assembly, maturation, and release of coronavirus virions.

22. Genes and proteins • Adaptability of coronaviruses • RNA-RNA recombination • High error rate of viral polymerase • Alter tissue tropism, host range, pathogenecity • SARS : dramatic demonstration of the adaptability of coronaviruses

24. Genes and proteins Fig. 19.6 In vitro assembly of genome cDNA and production of infectious genome RNA.

25. Apoptosis Autophagy Bronchitis Chimeric Encephalitis Endoplasmic reticulum- Golgi intermediate compartment (ERGIC) Gastroenteritis Hemagglutinin Hepatitis Hypoxemia Lectin Metalloproteinases Nested set Papain-like cysteine proteinases Class I fusion proteins Class II fusion proteins Coiled-coil Discontinuous transcription Peritonitis Picornavirus 3C proteinases Polyprotein Pseudoknot Replication complexes Replicative intermediate Reservoir Reverse genetics Sialic acid Subgenomic mRNA Syncytium Tropism Key Terms