Nuclear localisation of West Nile virus NS5 protein modulates host gene expression

Adam J. López-Denman; Daniel E. Tuipulotu; Jessica B. Ross; Alice M. Trenerry; Peter A. White; Jason M. Mackenzie

doi:10.1016/j.virol.2021.03.018

Nuclear localisation of West Nile virus NS5 protein modulates host gene expression

Adam J. López-Denman, Daniel E. Tuipulotu, Jessica B. Ross, Alice M. Trenerry, Peter A. White, Jason M. Mackenzie^*

^*Corresponding author for this work

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

5 Citations (Scopus)

Abstract

The involvement of the nucleus during flavivirus infection has been observed in only a small number of cases and can be limited to primarily two viral proteins; the structural protein C and the RNA polymerase NS5. Previously we observed that by blocking nuclear transport, WNV strain Kunjin (WNV_KUN) replication is severely affected and through mutation of the identified NLS in WNV_KUN NS5 protein. In this study, we interrogated the potential nuclear functions of WNV_KUN NS5 has on the host transcriptome, by means of RNA sequencing (RNAseq). In a direct comparison between wild type and mutant NS5, it can also be determined that the nuclear translocation of NS5 results in a significant down-regulation of host genes involved in the innate immune response. When compared to published RNAseq data from WNV infection, many of these genes were overlapping indicting the role of NS5 induced transcription during infection.

Original language	English
Pages (from-to)	131-144
Number of pages	14
Journal	Virology
Volume	559
DOIs	https://doi.org/10.1016/j.virol.2021.03.018
Publication status	Published - Jul 2021
Externally published	Yes

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10.1016/j.virol.2021.03.018

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@article{57de62f5c60d4cf2a1a4bdf2858c7589,

title = "Nuclear localisation of West Nile virus NS5 protein modulates host gene expression",

abstract = "The involvement of the nucleus during flavivirus infection has been observed in only a small number of cases and can be limited to primarily two viral proteins; the structural protein C and the RNA polymerase NS5. Previously we observed that by blocking nuclear transport, WNV strain Kunjin (WNVKUN) replication is severely affected and through mutation of the identified NLS in WNVKUN NS5 protein. In this study, we interrogated the potential nuclear functions of WNVKUN NS5 has on the host transcriptome, by means of RNA sequencing (RNAseq). In a direct comparison between wild type and mutant NS5, it can also be determined that the nuclear translocation of NS5 results in a significant down-regulation of host genes involved in the innate immune response. When compared to published RNAseq data from WNV infection, many of these genes were overlapping indicting the role of NS5 induced transcription during infection.",

keywords = "Gene expression, NS5, Next generation sequencing, Nucleus, RNA-Dependent RNA polymerase, RNAseq, West Nile virus",

author = "L{\'o}pez-Denman, {Adam J.} and Tuipulotu, {Daniel E.} and Ross, {Jessica B.} and Trenerry, {Alice M.} and White, {Peter A.} and Mackenzie, {Jason M.}",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = jul,

doi = "10.1016/j.virol.2021.03.018",

language = "English",

volume = "559",

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T1 - Nuclear localisation of West Nile virus NS5 protein modulates host gene expression

AU - López-Denman, Adam J.

AU - Tuipulotu, Daniel E.

AU - Ross, Jessica B.

AU - Trenerry, Alice M.

AU - White, Peter A.

AU - Mackenzie, Jason M.

PY - 2021/7

Y1 - 2021/7

N2 - The involvement of the nucleus during flavivirus infection has been observed in only a small number of cases and can be limited to primarily two viral proteins; the structural protein C and the RNA polymerase NS5. Previously we observed that by blocking nuclear transport, WNV strain Kunjin (WNVKUN) replication is severely affected and through mutation of the identified NLS in WNVKUN NS5 protein. In this study, we interrogated the potential nuclear functions of WNVKUN NS5 has on the host transcriptome, by means of RNA sequencing (RNAseq). In a direct comparison between wild type and mutant NS5, it can also be determined that the nuclear translocation of NS5 results in a significant down-regulation of host genes involved in the innate immune response. When compared to published RNAseq data from WNV infection, many of these genes were overlapping indicting the role of NS5 induced transcription during infection.

AB - The involvement of the nucleus during flavivirus infection has been observed in only a small number of cases and can be limited to primarily two viral proteins; the structural protein C and the RNA polymerase NS5. Previously we observed that by blocking nuclear transport, WNV strain Kunjin (WNVKUN) replication is severely affected and through mutation of the identified NLS in WNVKUN NS5 protein. In this study, we interrogated the potential nuclear functions of WNVKUN NS5 has on the host transcriptome, by means of RNA sequencing (RNAseq). In a direct comparison between wild type and mutant NS5, it can also be determined that the nuclear translocation of NS5 results in a significant down-regulation of host genes involved in the innate immune response. When compared to published RNAseq data from WNV infection, many of these genes were overlapping indicting the role of NS5 induced transcription during infection.

KW - Gene expression

KW - NS5

KW - Next generation sequencing

KW - Nucleus

KW - RNA-Dependent RNA polymerase

KW - RNAseq

KW - West Nile virus

UR - http://www.scopus.com/inward/record.url?scp=85104060480&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2021.03.018

DO - 10.1016/j.virol.2021.03.018

M3 - Article

SN - 0042-6822

VL - 559

SP - 131

EP - 144

JO - Virology

JF - Virology

ER -

Nuclear localisation of West Nile virus NS5 protein modulates host gene expression

Abstract

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