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Preface ix List of Abbreviations xi 1 The History of ZIKV Discovery 1 1.1 ZIKV Isolation from Monkeys and Mosquitos 1 1.2 ZIKV Infection in Humans 6 1.3 ZIKV Infection Spread to Other Hosts and Regions 7 1.4 Cross–Paths between ZIKV and Other Flaviviruses 9 References 10 2 ZIKV: From Silent to Epidemic 15 2.1 Outbreak in Yap Island (2007) 15 2.2 Outbreak in French Polynesia (2013) 16 2.3 How Did ZIKV Reach Brazil? 18 2.4 Outbreak in Brazil (2015) 18 2.5 ZIKV Spread through South, Central, and North Americas 20 References 22 3 ZIKV Transmission and Prevention 29 3.1 Modes of Transmission 29 3.2 Prevention 37 References 40 4 Association with Guillain]Barre Syndrome and Microcephaly 49 4.1 Association with Neurological Disorders 49 References 58 5 ZIKV Animal Models 69 5.1 Animal Models: Embryonated Hen Eggs 69 5.2 Animal Models: Landrace Piglet 69 5.3 Animal Models: Mice 70 5.4 Animal Model: Nonhuman Primate 74 References 78 6 Biology of ZIKV 83 6.1 Structural and Physical Properties of ZIKV Virion 84 6.2 Binding and Entry 87 6.3 Genome Structure 89 6.4 Translation and Proteolytic Processing 91 6.5 Features of the Nonstructural Proteins 92 6.6 RNA Replication 100 6.7 Features of the Structural Proteins 104 6.8 Virus Assembly and Release from Virus–Infected Cells 107 References 109 7 Zika Virus (ZIKV) Strains and Lineages 131 7.1 East and West African Lineage 131 7.2 Africa vs. Asian/American Lineage 132 References 140 8 ZIKV–Host Interactions 147 8.1 Systematic Studies to Identify ZIKV Affected Functions and Pathways 147 8.2 Induction and Dysregulation of Innate Immune Responses during ZIKV Infection 150 8.3 Induction of Cell Death and Apoptosis by ZIKV 156 8.4 Induction of Autophagy by ZIKV 160 8.5 Dysregulation of Cell Cycle and Induction of Abnormal Mitosis by ZIKV 163 References 164 9 Inhibitors of ZIKV Replication and Infection 179 9.1 Drugs That Lead to the Destruction of ZIKV Virions 179 9.2 Drugs That Inhibit ZIKV Entry and Endocytosis 180 9.3 Drugs That Target ZIKV NS2B–NS3 Protease Activity 186 9.4 Drugs That Target ZIKV NS5 RNA–Dependent RNA Polymerase Activity 191 9.5 Neutralizing Antibodies That Target ZIKV Structural Protein 200 9.6 Drugs That Inhibit ZIKV Infection by Targeting Host Machinery 201 9.7 Drugs That Show Neuroprotective Activity but Do Not Suppress ZIKV Replication: Emricasan 205 9.8 Other Drugs That Inhibit ZIKV Infection Identified from a Screening of FDA–Approved Drugs 206 References 210 10 Long–Term Care and Perspectives 229 10.1 Prenatal Care and Diagnosis of Abnormal Fetus Development 229 10.2 Long]Term Care for Patients Affected by ZIKV 230 10.3 Assistance to Families with Children Affected by ZIKV 230 10.4 Perspectives 231 References 232 Index 237