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Identification of diagnostic peptide regions that distinguish Zika virus from related mosquito-borne Flaviviruses.

ABSTRACT: 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 specificity, sensitivity, and surface exposure of each residue in relevant target proteins. For ZIKV we identified 104 and 116 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.

SUBMITTER: Lee AJ

PROVIDER: S-EPMC5451039 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Identification of diagnostic peptide regions that distinguish Zika virus from related mosquito-borne Flaviviruses.

Lee Alexandra J AJ Bhattacharya Roshni R Scheuermann Richard H RH Pickett Brett E BE

PloS one 20170531 5

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 Flaviv ...[more]

PMID: 28562637

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Project description:BackgroundIncreases in global travel and trade are changing arbovirus distributions worldwide. Arboviruses can be introduced by travelers, migratory birds, or vectors transported via international trade. Arbovirus surveillance in field-collected mosquitoes may provide early evidence for mosquito-borne disease transmission.MethodsDuring the seasons of high mosquito activity of 2018, 29,285 mosquitoes were sampled from seven sentinel sites in various insect regions. The mosquitoes were analyzed by RT-PCR for alphaviruses, flaviviruses, and orthobunyaviruses.ResultsWe detected three strains of Japanese encephalitis virus (JEV), five strains of Getah virus (GETV), and 45 strains of insect-specific flaviviruses including Aedes flavivirus (AeFV, 1), Chaoyang virus (CHAOV, 1), Culex flavivirus (CxFV, 17), Hanko virus (HANKV, 2), QuangBinh virus (QBV, 22), and Yunnan Culex flavivirus (YNCxFV, 2). Whole genomes of one strain each of GETV, CxFV, CHAOV, and AeFV were successfully amplified. Phylogenetic analysis revealed that the new JEV strains detected in the Shanghai and Hubei Provinces belong to the GI-b strain and are phylogenetically close to the NX1889 strain (MT134112) isolated from a patient during a JE outbreak in Ningxia in 2018. GETVs were found in Inner Mongolia, Hubei, and Hainan and belonged to Group III. They were closely related to strains isolated from swine. HANKV was recorded for the first time in China and other ISFVs were newly detected at several sentinel sites. The bias-corrected maximum likelihood estimation value for JEV in Jinshan, Shanghai was 4.52/1,000 (range 0.80-14.64). Hence, there is a potential risk of a JEV epidemic in that region.ConclusionGI-b is the dominant circulating JEV genotype in nature and poses a health risk to animals and humans. The potential threat of widespread GETV distribution as a zoonosis is gradually increasing. The present study also disclosed the dispersion and host range of ISFVs. These findings highlight the importance of tracing the movements of the vectors and hosts of mosquito-borne pathogens in order to prevent and control arbovirus outbreaks in China.

Dataset Information

Identification of diagnostic peptide regions that distinguish Zika virus from related mosquito-borne Flaviviruses.

Publications

Identification of diagnostic peptide regions that distinguish Zika virus from related mosquito-borne Flaviviruses.

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