Zika Virus Subgenomic Flavivirus RNA Generation Requires Cooperativity between Duplicated RNA Structures That Are Essential for Productive Infection in Human Cells.
3' Untranslated Regions
Aedes
Animals
Base Pairing
Base Sequence
Cell Line
Chlorocebus aethiops
Female
Genome, Viral
Host Specificity
Humans
Nucleic Acid Conformation
Phylogeny
RNA Stability
RNA, Viral
/ chemistry
Vero Cells
Virus Replication
Zika Virus
/ classification
Zika Virus Infection
/ virology
Zika virus
flavivirus
noncoding RNAs
sfRNAs
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
31 08 2020
31 08 2020
Historique:
received:
27
02
2020
accepted:
16
06
2020
pubmed:
26
6
2020
medline:
25
11
2020
entrez:
26
6
2020
Statut:
epublish
Résumé
Zika virus (ZIKV) is an emerging flavivirus, mainly transmitted by mosquitoes, which represents a global health threat. A common feature of flavivirus-infected cells is the accumulation of viral noncoding subgenomic RNAs by partial degradation of the viral genome, known as sfRNAs, involved in immune evasion and pathogenesis. Although great effort is being made to understand the mechanism by which these sfRNAs function during infection, the picture of how they work is still incomplete. In this study, we developed new genetic tools to dissect the functions of ZIKV RNA structures for viral replication and sfRNA production in mosquito and human hosts. ZIKV infections mostly accumulate two kinds of sfRNAs, sfRNA1 and sfRNA2, by stalling genome degradation upstream of duplicated stem loops (SLI and SLII) of the viral 3' untranslated region (UTR). Although the two SLs share conserved sequences and structures, different functions have been found for ZIKV replication in human and mosquito cells. While both SLs are enhancers for viral infection in human cells, they play opposite roles in the mosquito host. The dissection of determinants for sfRNA formation indicated a strong cooperativity between SLI and SLII, supporting a high-order organization of this region of the 3' UTR. Using recombinant ZIKV with different SLI and SLII arrangements, which produce different types of sfRNAs or lack the ability to generate these molecules, revealed that at least one sfRNA was necessary for efficient infection and transmission in
Identifiants
pubmed: 32581095
pii: JVI.00343-20
doi: 10.1128/JVI.00343-20
pmc: PMC7459552
pii:
doi:
Substances chimiques
3' Untranslated Regions
0
RNA, Viral
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI095175
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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