Genetic analysis of West Nile virus containing a complete 3'CSI RNA deletion

Bo Zhang; Hongping Dong; Hanqing Ye; Mark Tilgner; Pei Yong Shi

doi:10.1016/j.virol.2010.09.033

Genetic analysis of West Nile virus containing a complete 3'CSI RNA deletion

Bo Zhang, Hongping Dong, Hanqing Ye, Mark Tilgner, Pei Yong Shi

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

We report a genetic interplay among three pairs of long-distance RNA interactions that are involved in West Nile virus (WNV) genome cyclization and replication: 5'CS/3'CSI (conserved sequence), 5'UAR/3'UAR (upstream AUG region), and 5'DAR/3'DAR (downstream AUG region). Deletion of the complete 3'CSI element is lethal for WNV replication, but the replication of the 3'CSI deletion virus could be rescued by second site mutations. Functional analysis, using a genome-length RNA and replicon, mapped the compensatory mutations to the 5'UAR/3'UAR and 5'DAR/3'DAR regions. Biochemical analysis showed that the 3'CSI deletion abolished the 5' and 3' RNA interaction of the genome; the compensatory mutations could partially restore the 5' and 3' genome cyclization. These results demonstrate, for the first time, that a flavivirus without 3'CSI could restore genome cyclization and viral replication through enhancement of the 5'UAR/3'UAR and 5'DAR/3'DAR interactions.

Original language	English (US)
Pages (from-to)	138-145
Number of pages	8
Journal	Virology
Volume	408
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2010.09.033
State	Published - Dec 20 2010

Keywords

Cis RNA element
Flavivirus replication
RNA cyclization

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2010.09.033

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title = "Genetic analysis of West Nile virus containing a complete 3'CSI RNA deletion",

abstract = "We report a genetic interplay among three pairs of long-distance RNA interactions that are involved in West Nile virus (WNV) genome cyclization and replication: 5'CS/3'CSI (conserved sequence), 5'UAR/3'UAR (upstream AUG region), and 5'DAR/3'DAR (downstream AUG region). Deletion of the complete 3'CSI element is lethal for WNV replication, but the replication of the 3'CSI deletion virus could be rescued by second site mutations. Functional analysis, using a genome-length RNA and replicon, mapped the compensatory mutations to the 5'UAR/3'UAR and 5'DAR/3'DAR regions. Biochemical analysis showed that the 3'CSI deletion abolished the 5' and 3' RNA interaction of the genome; the compensatory mutations could partially restore the 5' and 3' genome cyclization. These results demonstrate, for the first time, that a flavivirus without 3'CSI could restore genome cyclization and viral replication through enhancement of the 5'UAR/3'UAR and 5'DAR/3'DAR interactions.",

keywords = "Cis RNA element, Flavivirus replication, RNA cyclization",

author = "Bo Zhang and Hongping Dong and Hanqing Ye and Mark Tilgner and Shi, {Pei Yong}",

note = "Funding Information: We thank Kristen Bernard for discussions and help during the course of this study. The work was partially supported by federal funds from the National Institute of Allergy and Infectious Disease, National Institutes of Health (NIH), under contract N01-AI-25490, by NIH grants 1U01AI061193 , AI061193 , and U54-AI057158 (Northeast Biodefense Center) to P.Y.S., as well as the 100 Talents Program from the Chinese Academy of Sciences and a grant from the Major State Basic Research Development Program of China (973 Program No. 2011CB504701 ) to B.Z.",

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AU - Dong, Hongping

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AU - Tilgner, Mark

AU - Shi, Pei Yong

N1 - Funding Information: We thank Kristen Bernard for discussions and help during the course of this study. The work was partially supported by federal funds from the National Institute of Allergy and Infectious Disease, National Institutes of Health (NIH), under contract N01-AI-25490, by NIH grants 1U01AI061193 , AI061193 , and U54-AI057158 (Northeast Biodefense Center) to P.Y.S., as well as the 100 Talents Program from the Chinese Academy of Sciences and a grant from the Major State Basic Research Development Program of China (973 Program No. 2011CB504701 ) to B.Z.

PY - 2010/12/20

Y1 - 2010/12/20

N2 - We report a genetic interplay among three pairs of long-distance RNA interactions that are involved in West Nile virus (WNV) genome cyclization and replication: 5'CS/3'CSI (conserved sequence), 5'UAR/3'UAR (upstream AUG region), and 5'DAR/3'DAR (downstream AUG region). Deletion of the complete 3'CSI element is lethal for WNV replication, but the replication of the 3'CSI deletion virus could be rescued by second site mutations. Functional analysis, using a genome-length RNA and replicon, mapped the compensatory mutations to the 5'UAR/3'UAR and 5'DAR/3'DAR regions. Biochemical analysis showed that the 3'CSI deletion abolished the 5' and 3' RNA interaction of the genome; the compensatory mutations could partially restore the 5' and 3' genome cyclization. These results demonstrate, for the first time, that a flavivirus without 3'CSI could restore genome cyclization and viral replication through enhancement of the 5'UAR/3'UAR and 5'DAR/3'DAR interactions.

AB - We report a genetic interplay among three pairs of long-distance RNA interactions that are involved in West Nile virus (WNV) genome cyclization and replication: 5'CS/3'CSI (conserved sequence), 5'UAR/3'UAR (upstream AUG region), and 5'DAR/3'DAR (downstream AUG region). Deletion of the complete 3'CSI element is lethal for WNV replication, but the replication of the 3'CSI deletion virus could be rescued by second site mutations. Functional analysis, using a genome-length RNA and replicon, mapped the compensatory mutations to the 5'UAR/3'UAR and 5'DAR/3'DAR regions. Biochemical analysis showed that the 3'CSI deletion abolished the 5' and 3' RNA interaction of the genome; the compensatory mutations could partially restore the 5' and 3' genome cyclization. These results demonstrate, for the first time, that a flavivirus without 3'CSI could restore genome cyclization and viral replication through enhancement of the 5'UAR/3'UAR and 5'DAR/3'DAR interactions.

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Genetic analysis of West Nile virus containing a complete 3'CSI RNA deletion

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