Structure of the thermally stable Zika virus

Victor A Kostyuchenko1,2, Elisa X Y Lim1,2, Shuijun Zhang1,2

  • 1Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.

Nature
|April 20, 2016
PubMed

Insights

The Zika virus (ZIKV) structure is similar to other flaviviruses but more compact and thermally stable. This stability may explain its survival in bodily fluids and suggests new therapeutic targets.

Area of Science:

  • Structural biology
  • Virology
  • Microbiology

Background:

  • Zika virus (ZIKV) is a pathogen linked to severe health issues like fetal microcephaly and Guillain-Barré syndrome.
  • Understanding ZIKV's structure is crucial for developing effective antiviral strategies.
  • Previous flavivirus research provides a comparative framework for ZIKV structural analysis.

Purpose of the Study:

  • To determine the high-resolution cryo-electron microscopy structure of the Zika virus.
  • To compare the ZIKV structure, particularly the envelope (E) protein, with other flaviviruses.
  • To investigate the structural stability of ZIKV and its implications for infectivity and transmission.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to resolve the ZIKV structure at 3.7 Å resolution.
  • Sequence and structural comparisons were performed between the ZIKV E protein and those of other flaviviruses (e.g., West Nile, Japanese encephalitis, Dengue).
  • Thermal stability assays and infectivity studies at varying temperatures were conducted.

Main Results:

  • The overall architecture of ZIKV is similar to other flaviviruses, but its structure is more compact.
  • Specific regions of the ZIKV envelope (E) protein show similarities to neurovirulent flaviviruses and Dengue virus (DENV).
  • ZIKV particles exhibit significant structural stability at 40°C, unlike less stable DENV serotypes, correlating with its infectivity.

Conclusions:

  • The structural stability of ZIKV may contribute to its survival in challenging environments like semen, saliva, and urine.
  • Targeting the ZIKV structure with antibodies or drugs that induce destabilization could be a viable therapeutic approach.
  • Further research into the E protein's role in flavivirus pathogenesis is warranted.