Yvonne (Bonnie) Maldonado, MD

1. 3/9/2016
ZikaVirus: Virology and
Relationship to Other Flaviviruses
Yvonne (Bonnie) Maldonado, MD

2.  Member of the Flaviviridae family of RNA viruses (more than 70 members)
• Include yellow fever, dengue, Japanese encephalitis, and West Nile viruses
• Most related to Spondweni virus
 Enveloped, spherical, ~50nm in diameter
 Single positive RNA strand genome ~10.8k nt
 Proteome: single polyprotein, co- and post-translational cleavage into 11
proteins
 Mature virions enclosed in a capsid and surrounded by a membrane
• Composed of a lipid bilayer, one RNA genome, three distinct viral proteins
‒ E: envelope protein; M: membrane proptein/prM – premembrane protein;
C: capid or core protein
3/9/2016Preparedness for the Zika Virus: A Public Health Emergency
Zika virus

3. 3/9/2016Preparedness for the Zika Virus: A Public Health Emergency

4. 3/9/2016Preparedness for the Zika Virus: A Public Health Emergency

5. Flavivirus E Protein
 The envelope (E) protein is the major surface protein
 E protein responsible for targeting virus to host cell receptors
 Followed by fusion of virus and cell membrane allowing viral cell entry
 E protein major target for human neutralizing antibodies, however, dengue
virus elicits ADE via antibodies to the prM protein
3/9/2016Preparedness for the Zika Virus: A Public Health Emergency

6. Flavivirus Life Cycle
3/9/2016Preparedness for the Zika Virus: A Public Health Emergency

7. Flavivirus Proteome
3/9/2016Preparedness for the Zika Virus: A Public Health Emergency

8. Heterogeneous Flavivirus Structural Proteins
3/9/2016Preparedness for the Zika Virus: A Public Health Emergency

9. Percentage homology of Zika virus (H/PF/2013) amino
acid identity with other flaviviruses
3/9/2016Preparedness for the Zika Virus: A Public Health Emergency

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T=3-like organization of surface dimers, membrane responsible
for development of immature to mature infectious virions

12. 3/9/2016Preparedness for the Zika Virus: A Public Health Emergency
Maturity, Infectivity, and Pathogenesis

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Zika Virology and Relationship to Disease

16. Important unknowns about Zika Virus Structure
 Dengue viruses are pleomorphic, is this true for Zika as well? Are there other
important differences compared to other flaviviruses?
• Variable prM content, temperature dependent transition, protein dynamics
 How do differences in Zika structure compared to dengue and other
flaviviruses affect the human immune response?
 How does Zika structure influence human cellular receptors, tropism, and cell
entry?
3/9/2016Preparedness for the Zika Virus: A Public Health Emergency

17. References
 http://www.viprbrc.org/brc/home.spg?decorator=flavi_zika
 Kuno et al, J Virology 1998, http://jvi.asm.org/content/72/1/73.full
 David M. Knipe, Peter M. Howley, et al. Fields’ Virology. 5th ed. 2007
Lippincott Williams & Wilkins, USA
3/9/2016Preparedness for the Zika Virus: A Public Health Emergency