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J Infect Dis. 2017 Dec 5;216(10):1196-1204. doi: 10.1093/infdis/jix473.

CD-loop Extension in Zika Virus Envelope Protein Key for Stability and Pathogenesis.

Author information

1
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill.
2
Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School.
3
Centre for BioImaging Science, National University of Singapore.
4
Department of Epidemiology, University of North Carolina at Chapel Hill.
5
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston.

Abstract

With severe disease manifestations including microcephaly, congenital malformation, and Guillain-Barré syndrome, Zika virus (ZIKV) remains a persistent global public health threat. Despite antigenic similarities with dengue viruses, structural studies have suggested the extended CD-loop and hydrogen-bonding interaction network within the ZIKV envelope protein contribute to stability differences between the viral families. This enhanced stability may lead to the augmented infection, disease manifestation, and persistence in body fluids seen following ZIKV infection. To examine the role of these motifs in infection, we generated a series of ZIKV recombinant viruses that disrupted the hydrogen-bonding network (350A, 351A, and 350A/351A) or the CD-loop extension (Δ346). Our results demonstrate a key role for the ZIKV extended CD-loop in cell-type-dependent replication, virion stability, and in vivo pathogenesis. Importantly, the Δ346 mutant maintains similar antigenicity to wild-type virus, opening the possibility for its use as a live-attenuated vaccine platform for ZIKV and other clinically relevant flaviviruses.

KEYWORDS:

Zika virus; cryo-electron microscopy; flavivirus; stability; structural virology

PMID:
28968838
PMCID:
PMC5853241
DOI:
10.1093/infdis/jix473
[Indexed for MEDLINE]
Free PMC Article

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