Identification of Diagnostic Peptide Regions that Distinguish Zika Virus from Related Mosquito-Borne Flaviviruses

Identification of Diagnostic Peptide Regions that Distinguish Zika Virus from Related Mosquito-Borne Flaviviruses

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Zika virus (ZIKV) is a member of the Flavivirus genus of positive-sense single-stranded RNA viruses, which includes Dengue, West Nile, Yellow Fever, and other mosquito-borne arboviruses. Infection by ZIKV can be difficult to distinguish from infection by other mosquito-borne Flaviviruses due to high sequence similarity, serum antibody cross-reactivity, and virus co-circulation in endemic areas. Indeed, existing serological methods are not able to consistently differentiate ZIKV from other Flaviviruses, which makes it extremely difficult to accurately calculate the incidence rate of Zika-associated Guillain-Barre in adults, microcephaly in newborns, or asymptomatic infections within a geographical area.

In order to identify Zika-specific peptide regions that could be used as serology reagents, we have applied comparative genomics and protein structure analyses to identify amino acid residues that distinguish each of 10 Flavivirus species and subtypes from each other by calculating the statistical significance, specificity, sensitivity, and surface exposure of each residue in relevant target proteins. For ZIKV we identified 129 and 131 15-mer peptides in the E glycoprotein and NS1 non-structural protein, respectively, that contain multiple diagnostic sites and are located in surface-exposed regions in the tertiary protein structure. These sensitive, specific, and surface-exposed peptide regions should serve as useful reagents for seroprevalence studies to better distinguish between prior infections with any of these mosquito-borne Flaviviruses.

The development of better detection methods and diagnostic tools will enable clinicians and public health workers to more accurately estimate the true incidence rate of asymptomatic infections, neurological syndromes, and birth defects associated with ZIKV infection.

Publications

Identification of diagnostic peptide regions that distinguish Zika virus from related mosquito-borne Flaviviruses.
PloS one. 2017-01-01; 12.6: e0178199.
PMID: 28562637

Funding

Research reported in this publication was supported by the National Institute Of Allergy and Infectious Diseases of the National Institutes of Health under Award Number U19AI110819 and contract no. HHSN272201400028C. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.