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Zika Virus by Mind Map: Zika Virus

1. Antivirals

1.1. No vaccine

1.2. No prophylaxis

1.3. Treatment

1.3.1. Symptom relief

1.4. Potential

1.4.1. IAA Attachment inhibitor Heparan sulfate-mimetic compound Entry inhibitor AXL antagonist TIM antagonist Internalization inhibitor Lipid modulators Fatty acid synthesis inhibitor Cholesterol synthesis inhibitor S1P inhibitor Autophagy inhibitor Lipophagy inhibitor Proteosome inhibitor Maturation inhibitor Furin inhibitor

1.4.2. DAA Fusion inhibitor E protein NS5 inhibitor RNA polymerase Multifunctional targets NS3 inhibitor NS1 NS4B inhibitor Prevent Mitochondria elongation Prevent interruption of innate immunity

2. Host-virus interactions

2.1. ER rearrangement

2.1.1. Vesicle Packets (VP) ER invaginations Site of RNA replication

2.1.2. Virus Bags (VB) Virions accumulate in regular arrays

2.1.3. Convoluted membranes (CMs) Unknown process NS3 enriched Polyprotein maturation

2.2. Lipophagy

2.2.1. Energy source of ER rearrangement

2.3. Mitochondria elongation

2.3.1. RIG-I-dependent interferon response

2.3.2. MAM disruption Mitochondria-associated membrane Contact site between ER & mitochondria Cellular homeostasis Lipid synthesis Protein degradation Energy Metabolism Innate immune signaling MAVS RLR

3. Questions

3.1. ZIKV in Canada?

3.2. How do you monitor ZIKV?

3.3. Treatment for ZIKV?

3.4. Translatable techniques from WNV to ZIKV

3.5. What is the role of bats in ZIKV ecology?

3.6. Why are there no cases of ZIKV in India?

3.6.1. How wide spread was the earlier outbreak in 1950?

3.6.2. How exposed was the Indian population in the first wave?

3.6.3. Life-long immunity against pandemic ZIKV?

3.7. Can asymptomatic individuals transmit ZIKV?

3.8. Why are some disease only reported in certain countries?

3.9. Impact of co-circulation of ZIKV and DENV?

3.9.1. How does a previous infection with DENV affect an individual with ZIKV?

3.10. Male infertility?

3.11. Economic burden of ZIKV syndrome

3.12. Is ZIKV a mosaic virus?

3.13. Co-localization of NS1 with NS4B? (+NS4A?)

3.14. Exosome-mediated transmission of infectious vRNA?

3.14.1. Method of entry to CNS & PNS?

3.15. How long does ZIKV immunity last?

4. Virus disease

4.1. Disease depends on portal of entry

4.2. Asymptomatic (~80%)

4.3. Symptomatic (~20%)

4.3.1. Misdiagnosed as DENV

4.3.2. Hemorrhagic

4.3.3. Autoimmune disease

4.3.4. Neurological disorders

4.3.5. Main Maculopapular rash Retro-orbital pain Low-grade fever Non-specific symptoms (ex. headache) Transient arthritis or arthralgia

4.4. Microcephaly

4.5. Transmission

4.5.1. Vector Same as blood transfusion Damage nervous system Brain inflammation Guillain-Barre syndrome Destruction of testes Reduce sperm count Reduce testosterone

4.5.2. Fluids Blood transfusion Saliva Urine

4.5.3. Sexual Semen (~6 months)

4.5.4. Vertical Placental macrophages Placental cells Impair placental function Apoptosis of neuroprogenitor cells

4.6. Cycles

4.6.1. Sylvatic (~0 incidence)

4.6.2. Endemic (moderate/low incidence)

4.6.3. Epidemic (high incidence)

4.6.4. Not at risk (importation)

4.7. Diagnostics

4.7.1. MS-base Detecting Quantitating NS1 Virions (M/E)

5. Virus Protein/Genome

5.1. Structural

5.1.1. Core

5.1.2. pr-M Serine residue Optimal cleavage site Fully cleaved

5.1.3. E AXL receptor

5.2. Non-structural

5.2.1. NS1 Multifunctional Dimer Modulate vRNA replication Organizational role Interact with pr-M & E Link VP with virion formation Hexamer Immune evasion Endothelial permeability

5.2.2. NS2B Co-factor

5.2.3. NS3 Protease Helicase

5.2.4. NS4A Organizational role

5.2.5. NS4B Inhibits activation of mitochondrial fission factor Disrupt fusion/fission equilibrium Dampens interferon response

5.2.6. NS5 RNA polymerase

6. Virus Lifecycle

6.1. Co-circulation

6.1.1. Similar symptoms

6.1.2. Misdiagnosis

6.1.3. DENV

6.1.4. CHIKV

6.1.5. YFV

6.2. Not in India

6.3. Attachment

6.3.1. GAG

6.3.2. DC-SIGN

6.4. Entry

6.4.1. PS receptor


6.4.3. TIM

6.5. Internalization

6.5.1. Clathrin-mediated endocytosis

6.6. Fusion

6.6.1. pH-dependent conformational change

6.6.2. E protein

6.7. Translation & replication

6.7.1. ER rearrangement

6.7.2. Fatty acids & cholesterol

6.7.3. Nucleotide biosynthesis

6.8. Trafficking & release

6.8.1. Maturation in TGN

6.8.2. Furin pr-M cleavage low pH

6.8.3. Secretory pathway