Post on 18-Jan-2017
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