Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper

Daniel A. Colón-Ramos, Pablo M. Irusta, Eugene C. Gan, Michael R. Olson, Jaewhan Song, Richard I. Morimoto, Richard M. Elliott, Mark Lombard, Robert Hollingsworth, J. Marie Hardwick, Gary K. Smith, Sally Kornbluth

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Members of the California serogroup of bunyaviruses (family Bunyaviridae) are the leading cause of pediatric viral encephalitis in North America. Significant cell death is observed as part of the infection pathology. We now report that a Bunyaviral nonstructural protein termed NSs shows sequence similarity to Reaper, a proapoptotic protein from Drosophila. Although NSs proteins lack the Reaper N-terminal motif critical for IAP inhibition, they do retain other functions of Reaper that map to conserved C-terminal regions. Like Reaper, NSs proteins induce mitochondrial cytochrome c release and caspase activation in cell-free extracts and promote neuronal apoptosis and mortality in a mouse model. Independent of caspase activation, Bunyavirus NSs proteins also share with Reaper the ability to directly inhibit cellular protein translation. We have found that the shared capacity to inhibit translation and induce apoptosis resides in common sequence motifs present in both Reaper and NSs proteins. Data presented here suggest that NSs induce apoptosis through a mechanism similar to that used by Reaper, as both proteins bind to an apoptotic regulator called Scythe and can relieve Scythe inhibition of Hsp70. Thus, bunyavirus NSs proteins have multiple Reaper-like functions that likely contribute to viral pathogenesis by promoting cell death and/or inhibiting cellular translation.

Original languageEnglish
Pages (from-to)4162-4172
Number of pages11
JournalMolecular Biology of the Cell
Volume14
Issue number10
DOIs
Publication statusPublished - 2003 Oct 1

Fingerprint

Orthobunyavirus
Apoptosis
Proteins
Caspases
Cell Death
Bunyaviridae
Viral Encephalitis
Mitochondrial Proteins
Protein Biosynthesis
North America
Cytochromes c
Cell Extracts
Pediatrics
Pathology
Mortality
Infection

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Colón-Ramos, Daniel A. ; Irusta, Pablo M. ; Gan, Eugene C. ; Olson, Michael R. ; Song, Jaewhan ; Morimoto, Richard I. ; Elliott, Richard M. ; Lombard, Mark ; Hollingsworth, Robert ; Hardwick, J. Marie ; Smith, Gary K. ; Kornbluth, Sally. / Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper. In: Molecular Biology of the Cell. 2003 ; Vol. 14, No. 10. pp. 4162-4172.
@article{d543f2161feb41f1b3ca6bf0890a9e14,
title = "Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper",
abstract = "Members of the California serogroup of bunyaviruses (family Bunyaviridae) are the leading cause of pediatric viral encephalitis in North America. Significant cell death is observed as part of the infection pathology. We now report that a Bunyaviral nonstructural protein termed NSs shows sequence similarity to Reaper, a proapoptotic protein from Drosophila. Although NSs proteins lack the Reaper N-terminal motif critical for IAP inhibition, they do retain other functions of Reaper that map to conserved C-terminal regions. Like Reaper, NSs proteins induce mitochondrial cytochrome c release and caspase activation in cell-free extracts and promote neuronal apoptosis and mortality in a mouse model. Independent of caspase activation, Bunyavirus NSs proteins also share with Reaper the ability to directly inhibit cellular protein translation. We have found that the shared capacity to inhibit translation and induce apoptosis resides in common sequence motifs present in both Reaper and NSs proteins. Data presented here suggest that NSs induce apoptosis through a mechanism similar to that used by Reaper, as both proteins bind to an apoptotic regulator called Scythe and can relieve Scythe inhibition of Hsp70. Thus, bunyavirus NSs proteins have multiple Reaper-like functions that likely contribute to viral pathogenesis by promoting cell death and/or inhibiting cellular translation.",
author = "Col{\'o}n-Ramos, {Daniel A.} and Irusta, {Pablo M.} and Gan, {Eugene C.} and Olson, {Michael R.} and Jaewhan Song and Morimoto, {Richard I.} and Elliott, {Richard M.} and Mark Lombard and Robert Hollingsworth and Hardwick, {J. Marie} and Smith, {Gary K.} and Sally Kornbluth",
year = "2003",
month = "10",
day = "1",
doi = "10.1091/mbc.E03-03-0139",
language = "English",
volume = "14",
pages = "4162--4172",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "10",

}

Colón-Ramos, DA, Irusta, PM, Gan, EC, Olson, MR, Song, J, Morimoto, RI, Elliott, RM, Lombard, M, Hollingsworth, R, Hardwick, JM, Smith, GK & Kornbluth, S 2003, 'Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper', Molecular Biology of the Cell, vol. 14, no. 10, pp. 4162-4172. https://doi.org/10.1091/mbc.E03-03-0139

Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper. / Colón-Ramos, Daniel A.; Irusta, Pablo M.; Gan, Eugene C.; Olson, Michael R.; Song, Jaewhan; Morimoto, Richard I.; Elliott, Richard M.; Lombard, Mark; Hollingsworth, Robert; Hardwick, J. Marie; Smith, Gary K.; Kornbluth, Sally.

In: Molecular Biology of the Cell, Vol. 14, No. 10, 01.10.2003, p. 4162-4172.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper

AU - Colón-Ramos, Daniel A.

AU - Irusta, Pablo M.

AU - Gan, Eugene C.

AU - Olson, Michael R.

AU - Song, Jaewhan

AU - Morimoto, Richard I.

AU - Elliott, Richard M.

AU - Lombard, Mark

AU - Hollingsworth, Robert

AU - Hardwick, J. Marie

AU - Smith, Gary K.

AU - Kornbluth, Sally

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Members of the California serogroup of bunyaviruses (family Bunyaviridae) are the leading cause of pediatric viral encephalitis in North America. Significant cell death is observed as part of the infection pathology. We now report that a Bunyaviral nonstructural protein termed NSs shows sequence similarity to Reaper, a proapoptotic protein from Drosophila. Although NSs proteins lack the Reaper N-terminal motif critical for IAP inhibition, they do retain other functions of Reaper that map to conserved C-terminal regions. Like Reaper, NSs proteins induce mitochondrial cytochrome c release and caspase activation in cell-free extracts and promote neuronal apoptosis and mortality in a mouse model. Independent of caspase activation, Bunyavirus NSs proteins also share with Reaper the ability to directly inhibit cellular protein translation. We have found that the shared capacity to inhibit translation and induce apoptosis resides in common sequence motifs present in both Reaper and NSs proteins. Data presented here suggest that NSs induce apoptosis through a mechanism similar to that used by Reaper, as both proteins bind to an apoptotic regulator called Scythe and can relieve Scythe inhibition of Hsp70. Thus, bunyavirus NSs proteins have multiple Reaper-like functions that likely contribute to viral pathogenesis by promoting cell death and/or inhibiting cellular translation.

AB - Members of the California serogroup of bunyaviruses (family Bunyaviridae) are the leading cause of pediatric viral encephalitis in North America. Significant cell death is observed as part of the infection pathology. We now report that a Bunyaviral nonstructural protein termed NSs shows sequence similarity to Reaper, a proapoptotic protein from Drosophila. Although NSs proteins lack the Reaper N-terminal motif critical for IAP inhibition, they do retain other functions of Reaper that map to conserved C-terminal regions. Like Reaper, NSs proteins induce mitochondrial cytochrome c release and caspase activation in cell-free extracts and promote neuronal apoptosis and mortality in a mouse model. Independent of caspase activation, Bunyavirus NSs proteins also share with Reaper the ability to directly inhibit cellular protein translation. We have found that the shared capacity to inhibit translation and induce apoptosis resides in common sequence motifs present in both Reaper and NSs proteins. Data presented here suggest that NSs induce apoptosis through a mechanism similar to that used by Reaper, as both proteins bind to an apoptotic regulator called Scythe and can relieve Scythe inhibition of Hsp70. Thus, bunyavirus NSs proteins have multiple Reaper-like functions that likely contribute to viral pathogenesis by promoting cell death and/or inhibiting cellular translation.

UR - http://www.scopus.com/inward/record.url?scp=10744231194&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744231194&partnerID=8YFLogxK

U2 - 10.1091/mbc.E03-03-0139

DO - 10.1091/mbc.E03-03-0139

M3 - Article

C2 - 14517326

AN - SCOPUS:10744231194

VL - 14

SP - 4162

EP - 4172

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 10

ER -