Comparative analysis of African and Asian/American Zika virus strains at the transcriptional and translational level
type: CreativeWork
description: Zika virus (ZIKV) is an emerging mosquito-borne flavivirus. Initially, ZIKV was considered of low importance as infection was usually asymptomatic or caused mild illness. However, the emergence of the Asian/American lineage, in contrast to the African lineage, was considered a public health threat. The Asian/American lineage has been associated with neurological complications such as Guillain-Barré syndrome in adults and congenital ZIKV syndrome (e.g., microcephaly) in newborns. Currently, it is not understood why this newly emerged Asian/American ZIKV results in a more severe disease than the African ZIKV. This project focused on understanding the molecular mechanisms underlying the differences in virulence and pathogenicity between these two ZIKV lineages in human brain cells. In order to identify the molecular determinants that influence viral replication and subsequent ZIKV virulence, the differences between an African and an American ZIKV strain were studied at different levels. Firstly, RNA-Seq and ribosome profiling (Ribo-Seq) was performed on astrocytoma-glioblastoma cells (U251 cells) infected with an African and an American ZIKV strain to determine the transcriptional and translational profile of each virus. Two previously overlooked upstream open reading frames (uORFs) in the 5′ untranslated region (UTR) of the American ZIKV genome were identified, initiating at non-canonical CUG and UUG codons; and a single uORF in the 5′UTR of the African ZIKV, initiating at a CUG start codon. The uORFs in the American ZIKV are referred to as ‘uORF1’ and ‘uORF2’, and the one in the African ZIKV as the ‘African uORF’. Secondly, considering their overlap with the main ORF, the viral polyprotein, it was hypothesised that these uORFs could play a role in the translational regulation of the main ORF. To investigate this, luciferase reporter assays were used, which showed that when the ZIKV 5′UTR harboured an African uORF or when uORF1 was not expressed, the main ORF was bett…
abstract: Zika virus (ZIKV) is an emerging mosquito-borne flavivirus. Initially, ZIKV was considered of low importance as infection was usually asymptomatic or caused mild illness. However, the emergence of the Asian/American lineage, in contrast to the African lineage, was considered a public health threat. The Asian/American lineage has been associated with neurological complications such as Guillain-Barré syndrome in adults and congenital ZIKV syndrome (e.g., microcephaly) in newborns. Currently, it is not understood why this newly emerged Asian/American ZIKV results in a more severe disease than the African ZIKV. This project focused on understanding the molecular mechanisms underlying the differences in virulence and pathogenicity between these two ZIKV lineages in human brain cells. In order to identify the molecular determinants that influence viral replication and subsequent ZIKV virulence, the differences between an African and an American ZIKV strain were studied at different levels. Firstly, RNA-Seq and ribosome profiling (Ribo-Seq) was performed on astrocytoma-glioblastoma cells (U251 cells) infected with an African and an American ZIKV strain to determine the transcriptional and translational profile of each virus. Two previously overlooked upstream open reading frames (uORFs) in the 5′ untranslated region (UTR) of the American ZIKV genome were identified, initiating at non-canonical CUG and UUG codons; and a single uORF in the 5′UTR of the African ZIKV, initiating at a CUG start codon. The uORFs in the American ZIKV are referred to as ‘uORF1’ and ‘uORF2’, and the one in the African ZIKV as the ‘African uORF’. Secondly, considering their overlap with the main ORF, the viral polyprotein, it was hypothesised that these uORFs could play a role in the translational regulation of the main ORF. To investigate this, luciferase reporter assays were used, which showed that when the ZIKV 5′UTR harboured an African uORF or when uORF1 was not expressed, the main ORF was bett…
author: Lefèvre, Charlotte
language: eng
keywords: Ribosome profiling, uORF, Zika virus
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/326cc8a8-6bfa-495e-a88c-cecd661b5121/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-06-29
date modified: 2026-07-22T22:24:07Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.105866