Nuclear localization and secretion competence are conserved among henipavirus matrix proteins

Elisabeth C. McLinton, Kylie M. Wagstaff, Alexander Lee, Gregory W. Moseley, Glenn A. Marsh, Lin-Fa Wang, David A. Jans, Kim G. Lieu, Hans J. Netter

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Viruses of the genus Henipavirus of the family Paramyxoviridae are zoonotic pathogens, which have emerged in Southeast Asia, Australia and Africa. Nipah virus (NiV) and Hendra virus are highly virulent pathogens transmitted from bats to animals and humans, while the henipavirus Cedar virus seems to be non-pathogenic in infection studies. The full replication cycle of the Paramyxoviridae occurs in the host cell’s cytoplasm, where viral assembly is orchestrated by the matrix (M) protein. Unexpectedly, the NiV-M protein traffics through the nucleus as an essential step to engage the plasma membrane in preparation for viral budding/release. Comparative studies were performed to assess whether M protein nuclear localization is a common feature of the henipaviruses, including the recently sequenced (although not yet isolated) Ghanaian bat henipavirus (Kumasi virus, GH-M74a virus) and Mojiang virus. Live-cell confocal microscopy revealed that nuclear translocation of GFP-fused M protein is conserved between henipaviruses in both human- and bat-derived cell lines. However, the efficiency of M protein nuclear localization and virus-like particle budding competency varied. Additionally, Cedar virus-, Kumasi virus- and Mojiang virus-M proteins were mutated in a bipartite nuclear localization signal, indicating that a key lysine residue is essential for nuclear import, export and induction of budding events, as previously reported for NiV-M. The results of this study suggest that the M proteins of henipaviruses may utilize a similar nucleocytoplasmic trafficking pathway as an essential step during viral replication in both humans and bats.

Original languageEnglish
Pages (from-to)563-576
Number of pages14
JournalJournal of General Virology
Volume98
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017

Keywords

  • Hendra virus
  • Henipavirus
  • Matrix protein
  • Nipah virus
  • Nuclear localization
  • Virus-like particle

Cite this

McLinton, Elisabeth C. ; Wagstaff, Kylie M. ; Lee, Alexander ; Moseley, Gregory W. ; Marsh, Glenn A. ; Wang, Lin-Fa ; Jans, David A. ; Lieu, Kim G. ; Netter, Hans J. / Nuclear localization and secretion competence are conserved among henipavirus matrix proteins. In: Journal of General Virology. 2017 ; Vol. 98, No. 4. pp. 563-576.
@article{e495ccd9d64b44ff9c400eae90a8b041,
title = "Nuclear localization and secretion competence are conserved among henipavirus matrix proteins",
abstract = "Viruses of the genus Henipavirus of the family Paramyxoviridae are zoonotic pathogens, which have emerged in Southeast Asia, Australia and Africa. Nipah virus (NiV) and Hendra virus are highly virulent pathogens transmitted from bats to animals and humans, while the henipavirus Cedar virus seems to be non-pathogenic in infection studies. The full replication cycle of the Paramyxoviridae occurs in the host cell’s cytoplasm, where viral assembly is orchestrated by the matrix (M) protein. Unexpectedly, the NiV-M protein traffics through the nucleus as an essential step to engage the plasma membrane in preparation for viral budding/release. Comparative studies were performed to assess whether M protein nuclear localization is a common feature of the henipaviruses, including the recently sequenced (although not yet isolated) Ghanaian bat henipavirus (Kumasi virus, GH-M74a virus) and Mojiang virus. Live-cell confocal microscopy revealed that nuclear translocation of GFP-fused M protein is conserved between henipaviruses in both human- and bat-derived cell lines. However, the efficiency of M protein nuclear localization and virus-like particle budding competency varied. Additionally, Cedar virus-, Kumasi virus- and Mojiang virus-M proteins were mutated in a bipartite nuclear localization signal, indicating that a key lysine residue is essential for nuclear import, export and induction of budding events, as previously reported for NiV-M. The results of this study suggest that the M proteins of henipaviruses may utilize a similar nucleocytoplasmic trafficking pathway as an essential step during viral replication in both humans and bats.",
keywords = "Hendra virus, Henipavirus, Matrix protein, Nipah virus, Nuclear localization, Virus-like particle",
author = "McLinton, {Elisabeth C.} and Wagstaff, {Kylie M.} and Alexander Lee and Moseley, {Gregory W.} and Marsh, {Glenn A.} and Lin-Fa Wang and Jans, {David A.} and Lieu, {Kim G.} and Netter, {Hans J.}",
year = "2017",
month = "4",
day = "1",
doi = "10.1099/jgv.0.000703",
language = "English",
volume = "98",
pages = "563--576",
journal = "Journal of General Virology",
issn = "0022-1317",
publisher = "Microbiology Society",
number = "4",

}

Nuclear localization and secretion competence are conserved among henipavirus matrix proteins. / McLinton, Elisabeth C.; Wagstaff, Kylie M.; Lee, Alexander; Moseley, Gregory W.; Marsh, Glenn A.; Wang, Lin-Fa; Jans, David A.; Lieu, Kim G.; Netter, Hans J.

In: Journal of General Virology, Vol. 98, No. 4, 01.04.2017, p. 563-576.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Nuclear localization and secretion competence are conserved among henipavirus matrix proteins

AU - McLinton, Elisabeth C.

AU - Wagstaff, Kylie M.

AU - Lee, Alexander

AU - Moseley, Gregory W.

AU - Marsh, Glenn A.

AU - Wang, Lin-Fa

AU - Jans, David A.

AU - Lieu, Kim G.

AU - Netter, Hans J.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Viruses of the genus Henipavirus of the family Paramyxoviridae are zoonotic pathogens, which have emerged in Southeast Asia, Australia and Africa. Nipah virus (NiV) and Hendra virus are highly virulent pathogens transmitted from bats to animals and humans, while the henipavirus Cedar virus seems to be non-pathogenic in infection studies. The full replication cycle of the Paramyxoviridae occurs in the host cell’s cytoplasm, where viral assembly is orchestrated by the matrix (M) protein. Unexpectedly, the NiV-M protein traffics through the nucleus as an essential step to engage the plasma membrane in preparation for viral budding/release. Comparative studies were performed to assess whether M protein nuclear localization is a common feature of the henipaviruses, including the recently sequenced (although not yet isolated) Ghanaian bat henipavirus (Kumasi virus, GH-M74a virus) and Mojiang virus. Live-cell confocal microscopy revealed that nuclear translocation of GFP-fused M protein is conserved between henipaviruses in both human- and bat-derived cell lines. However, the efficiency of M protein nuclear localization and virus-like particle budding competency varied. Additionally, Cedar virus-, Kumasi virus- and Mojiang virus-M proteins were mutated in a bipartite nuclear localization signal, indicating that a key lysine residue is essential for nuclear import, export and induction of budding events, as previously reported for NiV-M. The results of this study suggest that the M proteins of henipaviruses may utilize a similar nucleocytoplasmic trafficking pathway as an essential step during viral replication in both humans and bats.

AB - Viruses of the genus Henipavirus of the family Paramyxoviridae are zoonotic pathogens, which have emerged in Southeast Asia, Australia and Africa. Nipah virus (NiV) and Hendra virus are highly virulent pathogens transmitted from bats to animals and humans, while the henipavirus Cedar virus seems to be non-pathogenic in infection studies. The full replication cycle of the Paramyxoviridae occurs in the host cell’s cytoplasm, where viral assembly is orchestrated by the matrix (M) protein. Unexpectedly, the NiV-M protein traffics through the nucleus as an essential step to engage the plasma membrane in preparation for viral budding/release. Comparative studies were performed to assess whether M protein nuclear localization is a common feature of the henipaviruses, including the recently sequenced (although not yet isolated) Ghanaian bat henipavirus (Kumasi virus, GH-M74a virus) and Mojiang virus. Live-cell confocal microscopy revealed that nuclear translocation of GFP-fused M protein is conserved between henipaviruses in both human- and bat-derived cell lines. However, the efficiency of M protein nuclear localization and virus-like particle budding competency varied. Additionally, Cedar virus-, Kumasi virus- and Mojiang virus-M proteins were mutated in a bipartite nuclear localization signal, indicating that a key lysine residue is essential for nuclear import, export and induction of budding events, as previously reported for NiV-M. The results of this study suggest that the M proteins of henipaviruses may utilize a similar nucleocytoplasmic trafficking pathway as an essential step during viral replication in both humans and bats.

KW - Hendra virus

KW - Henipavirus

KW - Matrix protein

KW - Nipah virus

KW - Nuclear localization

KW - Virus-like particle

UR - http://www.scopus.com/inward/record.url?scp=85019169053&partnerID=8YFLogxK

U2 - 10.1099/jgv.0.000703

DO - 10.1099/jgv.0.000703

M3 - Article

VL - 98

SP - 563

EP - 576

JO - Journal of General Virology

JF - Journal of General Virology

SN - 0022-1317

IS - 4

ER -