05/01/2023

ZikaVirus: Virology and Relationship to Other Flaviviruses Yvonne (Bonnie) Maldonado, MD

05/01/2023

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

Preparedness for the Zika Virus: A Public Health Emergency

Zika virus

05/01/2023Preparedness for the Zika Virus: A Public Health Emergency

05/01/2023Preparedness for the Zika Virus: A Public Health Emergency

05/01/2023

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

Preparedness for the Zika Virus: A Public Health Emergency

05/01/2023

Flavivirus Life Cycle

Preparedness for the Zika Virus: A Public Health Emergency

05/01/2023

Flavivirus Proteome

Preparedness for the Zika Virus: A Public Health Emergency

05/01/2023

Heterogeneous Flavivirus Structural Proteins

Preparedness for the Zika Virus: A Public Health Emergency

05/01/2023

Percentage homology of Zika virus (H/PF/2013) amino acid identity with other

flaviviruses

Preparedness for the Zika Virus: A Public Health Emergency

05/01/2023Preparedness for the Zika Virus: A Public Health Emergency

05/01/2023Preparedness for the Zika Virus: A Public Health Emergency

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

05/01/2023Preparedness for the Zika Virus: A Public Health Emergency

Maturity, Infectivity, and Pathogenesis

05/01/2023Preparedness for the Zika Virus: A Public Health Emergency

05/01/2023Preparedness for the Zika Virus: A Public Health Emergency

05/01/2023Preparedness for the Zika Virus: A Public Health Emergency

Zika Virology and Relationship to Disease

05/01/2023

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?

Preparedness for the Zika Virus: A Public Health Emergency

05/01/2023

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

Preparedness for the Zika Virus: A Public Health Emergency