Chikungunya Virus

Description

This book provides readers with a collection of latest reviews written by Chikungunya virus (CHIKV) research leaders who cover topics related to CHIKV replication, advances in CHIKV research reagents and model system development, as well as the pathogenesis of chronic CHIKV disease. Moreover, the volume updates on recent progress in the development of therapeutics and vaccines for treatment and prevention of CHIKV-induced disease. Chikungunya virus (CHIKV) is a mosquito-borne pathogen that has re-emerged to become a significant global disease threat.  Although CHIKV has historically been associated with localized outbreaks of debilitating polyarthralgia in Africa and Asia, factors such as increased global travel and viral adaptation to new mosquito vectors have led to the introduction and spread of CHIKV in new regions of the world, including the Americas.  The re-emergence of CHIKV has stimulated significant interest both in understanding the biology of CHIKV and in the development of medical countermeasures against the virus. Preface Contents 146 Molecular Virology of Chikungunya Virus Abstract 1 Introduction 2 Chikungunya Virus Genome and Cis-Acting Sequence Elements 3 Alphavirus Nonstructural Proteins and Regulation of RNA Synthesis 3.1 Nonstructural Polyprotein Synthesis and Processing 3.2 Functions of Alphavirus Nonstructural Proteins in RNA Synthesis and Virus–Host Interactions 3.2.1 Nonstructural Protein 1, nsP1 3.2.2 Nonstructural Protein 2, nsP2 3.2.3 Nonstructural Protein 3, nsP3 3.2.4 Nonstructural Protein 4, nsP4 4 Replication Complexes 4.1 Compartments of Alphavirus RNA Replication 4.2 Assembly of Viral Replication Complexes 5 Conclusions References 158 Understanding Molecular Pathogenesis with Chikungunya Virus Research Tools Abstract 1 Chikungunya Virus and Disease 2 Chikungunya Virus Molecular Tools 3 Aedes Mosquito Vectors 3.1 Aedes Mosquito In Vitro Cell Line Systems 3.2 In Vivo Studies in Mosquito Vectors 4 Mammalian Hosts 4.1 Viral Proteins Functions and Mechanisms of Replication 4.2 Genome-Wide Screens and Targeting the Mammalian Host 4.3 Human Patient Cohorts and Immune Mediators 4.4 Protective Immunity in Animal Models 4.5 Innate Immunity in Animal Models 4.6 Development and Assessment of Therapeutics in Animal Models 5 Conclusions References 147 Chronic Chikungunya Virus Disease Abstract 1 Introduction 2 What Is Chronic CHIKV Disease? 3 When and Where Has Chronic Disease Associated with CHIKV Infection Been Observed? 4 Frequency of Chronic CHIKV Disease Manifestations 5 Disease Signs and Symptoms of Post-acute CHIKV Disease 6 Risk Factors for Chronic CHIKV Disease 7 Immunological Characteristics of Chronic CHIKV Disease 7.1 T Cells 7.2 NK Cells 7.3 Monocytes and Macrophages 7.4 B Cells and Antibody 7.5 Cytokines and Chemokines 8 Therapeutic Interventions for Chronic CHIKV Disease 9 Mechanisms of Chronic Disease Pathogenesis 9.1 Autoimmunity 9.2 Persistence of Viral Replication, Viral PAMPs, and/or Viral Antigen Acknowledgements References 175 Chikungunya Virus Vaccines: Platforms, Progress, and Challenges Abstract 1 Introduction: Chikungunya Ecology and Economic Impact 2 CHIKV Replication and Immune Reactivity 3 Animal Models of CHIKV Infection and Immunity 4 Vaccine Technology Classes 4.1 Live Attenuated Viral Vaccines 4.2 Chimeric Viral Vector Platforms 4.3 Inert Antigen Vaccines 4.4 Nucleic Acid Based Vaccines 5 Priorities for and Barriers to Clinical CHIKV Vaccine Development References 195 Small Molecule Inhibitors Targeting Chikungunya Virus Abstract 1 Introduction 2 CHIKV Genome Organization and Replication Cycle 3 Methods for Identifying Small Molecule Inhibitors Against CHIKV 4 Small Molecule Inhibitor Strategies for Targeting CHIKV 4.1 Inhibitors of CHIKV Entry 4.2 Inhibitors of CHIKV Structural Proteins 4.3 Inhibitors of CHIKV Non-structural Proteins 4.3.1 nsP1 4.3.2 nsP2 4.3.3 nsP3 4.3.4 nsP4 4.4 Inhibitors of CHIKV RNA Genome Replication 5 Targeting Host Factors Involved in CHIKV Replication 5.1 Protease Inhibitors 5.2 Pyrimidine and Purine Synthesis Inhibitors 5.3 Cellular Kinase Inhibitors 5.4 Inhibitors of Protein Chaperones 6 Conclusions Acknowledgements References