Front Cover

Coronaviruses

Copyright

In Memoriam

Contents

Contributors

Preface

Chapter One: Supramolecular Architecture of the Coronavirus Particle

1. Introduction

2. Virion Structure and Durability

3. Viral Proteins in Assembly and Fusion

3.1. Membrane Protein

3.2. Nucleoprotein

3.3. Envelope Protein

3.4. Spike Protein

4. Evolution of the Structural Proteins

References

Chapter Two: Coronavirus Spike Protein and Tropism Changes

1. Introduction

2. Structure of the Coronavirus S Protein

2.1. Structure of the S1 Subunit

2.2. Structure of the S2 Subunit

3. Spike-Receptor Interactions

3.1. Different Domains Within S1 May Act as RBD

3.2. CoV Protein Receptor Preference

4. S Protein Proteolytic Cleavage and Conformational Changes

5. Tropism Changes Associated with S Protein Mutations

5.1. S1 Receptor Interactions Determining Tropism

5.1.1. S1 NTR Changes

5.1.2. S1 CTR Changes

5.2. Changes in Proteolytic Cleavage Site and Other S2 Mutations Associated with Altered Tropism

5.2.1. Changes in Proteolytic Cleavage Sites

5.2.2. Other S2 Mutations Associated with Altered Tropism

6. Concluding Remarks

Acknowledgments

References

Chapter Three: The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing

1. Introduction

2. Coronavirus nsp7-10: Small but Critical Regulatory Subunits?

2.1. Coronavirus nsp7

2.2. Coronavirus nsp8 and nsp7-nsp8 Complexes

2.3. Coronavirus nsp9

2.4. Coronavirus nsp10

3. Coronavirus nsp12: A Multidomain RNA Polymerase

3.1. The nsp12 RdRp Domain

3.2. The Initiation Mechanism of the nsp12 RdRp

3.3. Inhibitors of the nsp12 RdRp

3.4. The nsp12 NiRAN Domain

4. Coronavirus nsp13: A Multifunctional and Highly Conserved Helicase Subunit

4.1. The Coronavirus nsp13 SF1 Helicase (HEL1)

4.2. The Helicase-Associated ZBD

4.3. Nidovirus Helicase Structural Biology

4.4. Functional Characterization of the Nidovirus Helicase

4.5. The Coronavirus Helicase as Drug Target

5. The Coronavirus Capping Machinery: nsp10-13-14-16

5.1. The nsp13 RNA 5' Triphosphatase

5.2. The Elusive RNA GTase

5.3. The nsp14 N7-Methyl Transferase

5.4. The nsp16 2'-O-Methyl Transferase

6. Coronavirus nsp14 ExoN: Key to a Unique Mismatch Repair Mechanism That Promotes Fidelity

7. Coronavirus nsp15: A Remarkable Endoribonuclease with Elusive Functions

8. Summary and Future Perspectives

Acknowledgments

References

Chapter Four: Coronavirus cis-Acting RNA Elements

1. Introduction

2. Coronavirus Genome Replication and Transcription

3. Coronavirus cis-Acting RNA Elements

3.1. 5-Terminal cis-Acting RNA Elements

3.1.1. Structural Features of Coronavirus 5'-Terminal cis-Acting Elements

3.1.2. Functional Roles of Coronavirus 5'-Terminal cis-Acting Elements

3.1.2.1. Stem-Loops 1 and 2

3.1.2.2. Stem-Loop 3

3.1.2.3. Stem-Loop 4

3.1.2.4. Stem-Loop 5

3.2. 3'-Terminal cis-Acting RNA Elements

3.2.1. Structural Features of Coronavirus 3' cis-Acting Elements

3.2.2. Functional Roles of Coronavirus 3'-Terminal cis-Acting Elements

3.2.2.1. BSL and Pseudoknot

3.2.2.2. Hypervariable Region

3.2.2.3. 3'-Terminal Poly(A) Tail

4. RNA Elements Involved in Coronavirus Genome Packaging

5. Possible Roles of Cellular Proteins in Coronavirus Replication

6. Conclusions and Outlook

Acknowledgments

References

Chapter Five: Viral and Cellular mRNA Translation in Coronavirus-Infected Cells

1. Introduction

1.1. Overview of Translation Mechanism in Animal Cells

1.2. CoVs

1.3. Overview of CoV Genome Organization and Gene Expression Strategy

2. Mechanisms and Control of Translation of Coronavirus mRNAs

2.1. Evidence for Cap-Dependent Translation of CoV mRNAs

2.2. Viral Enzymes Involved in Capping of CoV mRNAs

2.3. Changes in the Poly(A) Tail Length During CoV Replication

2.4. Ribosomal Frameshift in CoV Gene 1 Protein Expression

2.5. Ribosomal Shunting Mechanism of Translation in CoVs

2.6. Leaky Scanning Translation Mechanism of CoV Internal ORFs

2.7. IRES-Mediated Translation in CoVs

2.8. Presence of Upstream ORF in CoV Genomic RNAs

3. Host and Viral Factors That Regulate Coronavirus mRNA Translation

3.1. Factors That Bind to Viral UTRs

3.2. N Protein-Mediated Enhancement of Viral Translation

4. Coronavirus-Mediated Control of Host Translation

4.1. CoV Proteins That Suppress Translation

4.2. CoV-Mediated Induction of ER Stress and Unfolded Protein Response

4.3. Status of Stress Granules and Processing Bodies in CoV Replication

4.4. Activation of PKR, PERK, and eIF2α Phosphorylation

5. Concluding Remarks

Acknowledgments

References

Chapter Six: Feline Coronaviruses: Pathogenesis of Feline Infectious Peritonitis

1. Feline Coronaviruses

1.1. Taxonomy and Genome Organization

1.2. Accessory Genes and Proteins

1.3. FCoV Serotypes and Cellular Receptor Usage

2. Infection with Feline Coronaviruses

2.1. Feline Enteric Coronavirus

2.2. Feline Infectious Peritonitis Virus

2.3. Origin of FIPV

3. Molecular Pathogenesis of FIP

3.1. Differences Between FECV and FIPV

4. Reverse Genetics of Feline Coronaviruses

5. Perspectives

References

Chapter Seven: Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response

1. Introduction

2. The Coronavirus Genome

3. The Type I IFN System

3.1. Types of IFNs and Their Signaling Pathways

3.2. Induction of Type I IFNs

3.3. IFN-Stimulated Gene Expression

4. Antiviral Action of IFNs Against Human Coronaviruses

5. Evasion Strategies of Coronaviruses

5.1. Inhibition of IFN Induction

5.2. Inhibition of IFN Signaling

5.3. Increasing IFN Resistance

6. Conclusions and Outlook

Acknowledgments

References

Chapter Eight: Molecular Basis of Coronavirus Virulence and Vaccine Development

1. Introduction

1.1. Focus of the Review

1.2. CoV Genome Structure and Protein Composition

1.3. Requirement of B- and T-Cell Responses for Protection

1.4. Antigenic Complexity of SARS- and MERS-CoV

1.5. Animal Models for CoV Vaccine and Antivirals Studies

2. Subunit, Inactivated, and Vectored Vaccines

2.1. Subunit Vaccines

2.2. Vaccines Based on Inactivated Whole Virus

2.3. Vectored Vaccines

3. Live-Attenuated Vaccines

3.1. Strategies to Engineer Attenuated CoVs as Vaccine Candidates

3.2. Coronavirus Virulence

3.3. IFN Sensitivity of Human CoVs

3.4. Innate Immunity Modulators Encoded by Common Human CoVs

3.5. SARS-CoV Genes as Modulators of the Innate Immune Response

3.6. MERS-CoV Genes as Modulators of the Innate Immune Response

4. Vaccine Biosafety

4.1. ADEI and Eosinophilia Induction

4.2. Interaction of CoV Vaccine Candidates with Cells of the Immune System

5. Coronavirus Antiviral Selection

6. Conclusions

Acknowledgments

References

Index

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