Alphavirus-induced apoptosis in mouse brains correlates with neurovirulence

Jennifer Lewis, Steven L. Wesselingh, Diane Griffin, J Marie Hardwick

Research output: Contribution to journalArticle

Abstract

Sindbis virus induces apoptotic cell death in cultured cell lines, raising the possibility that apoptosis of infected neurons and other target cells in vivo may contribute to the resulting disease and mortality. To investigate the role of apoptosis in Sindbis virus pathogenesis, infected mouse brains were assayed by the in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling technique and for DNA ladder formation. Infection with recombinant Sindbis virus strain 633 resulted in widespread apoptosis in newborn mouse brains and spinal cords, but few apoptotic cells were observed following infection of 2-week-old animals. This finding correlates with the age-dependent mortality observed in mice. The more neurovirulent virus TE, which differs from 633 by a single amino acid in the E2 glycoprotein, induced significant apoptosis in brains and spinal cords of 2-week-old animals, consistent with its ability to cause fatal disease in older animals. Double- labeling experiments demonstrated that the apoptotic cells were also infected with Sindbis virus. Thus, Sindbis virus-induced apoptosis appears to be a direct result of virus infection and is likely to reflect pathogenic mechanisms for other viruses.

Original languageEnglish (US)
Pages (from-to)1828-1835
Number of pages8
JournalJournal of Virology
Volume70
Issue number3
StatePublished - 1996

Fingerprint

Sindbis virus
Sindbis Virus
Alphavirus
apoptosis
Apoptosis
brain
mice
Brain
spinal cord
viruses
Spinal Cord
infection
Viruses
labeling techniques
ladders
DNA Nucleotidylexotransferase
Mortality
Virus Diseases
cells
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Alphavirus-induced apoptosis in mouse brains correlates with neurovirulence. / Lewis, Jennifer; Wesselingh, Steven L.; Griffin, Diane; Hardwick, J Marie.

In: Journal of Virology, Vol. 70, No. 3, 1996, p. 1828-1835.

Research output: Contribution to journalArticle

Lewis, Jennifer ; Wesselingh, Steven L. ; Griffin, Diane ; Hardwick, J Marie. / Alphavirus-induced apoptosis in mouse brains correlates with neurovirulence. In: Journal of Virology. 1996 ; Vol. 70, No. 3. pp. 1828-1835.
@article{ad896a62ea2549a58a7c5991235f8e8c,
title = "Alphavirus-induced apoptosis in mouse brains correlates with neurovirulence",
abstract = "Sindbis virus induces apoptotic cell death in cultured cell lines, raising the possibility that apoptosis of infected neurons and other target cells in vivo may contribute to the resulting disease and mortality. To investigate the role of apoptosis in Sindbis virus pathogenesis, infected mouse brains were assayed by the in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling technique and for DNA ladder formation. Infection with recombinant Sindbis virus strain 633 resulted in widespread apoptosis in newborn mouse brains and spinal cords, but few apoptotic cells were observed following infection of 2-week-old animals. This finding correlates with the age-dependent mortality observed in mice. The more neurovirulent virus TE, which differs from 633 by a single amino acid in the E2 glycoprotein, induced significant apoptosis in brains and spinal cords of 2-week-old animals, consistent with its ability to cause fatal disease in older animals. Double- labeling experiments demonstrated that the apoptotic cells were also infected with Sindbis virus. Thus, Sindbis virus-induced apoptosis appears to be a direct result of virus infection and is likely to reflect pathogenic mechanisms for other viruses.",
author = "Jennifer Lewis and Wesselingh, {Steven L.} and Diane Griffin and Hardwick, {J Marie}",
year = "1996",
language = "English (US)",
volume = "70",
pages = "1828--1835",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - Alphavirus-induced apoptosis in mouse brains correlates with neurovirulence

AU - Lewis, Jennifer

AU - Wesselingh, Steven L.

AU - Griffin, Diane

AU - Hardwick, J Marie

PY - 1996

Y1 - 1996

N2 - Sindbis virus induces apoptotic cell death in cultured cell lines, raising the possibility that apoptosis of infected neurons and other target cells in vivo may contribute to the resulting disease and mortality. To investigate the role of apoptosis in Sindbis virus pathogenesis, infected mouse brains were assayed by the in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling technique and for DNA ladder formation. Infection with recombinant Sindbis virus strain 633 resulted in widespread apoptosis in newborn mouse brains and spinal cords, but few apoptotic cells were observed following infection of 2-week-old animals. This finding correlates with the age-dependent mortality observed in mice. The more neurovirulent virus TE, which differs from 633 by a single amino acid in the E2 glycoprotein, induced significant apoptosis in brains and spinal cords of 2-week-old animals, consistent with its ability to cause fatal disease in older animals. Double- labeling experiments demonstrated that the apoptotic cells were also infected with Sindbis virus. Thus, Sindbis virus-induced apoptosis appears to be a direct result of virus infection and is likely to reflect pathogenic mechanisms for other viruses.

AB - Sindbis virus induces apoptotic cell death in cultured cell lines, raising the possibility that apoptosis of infected neurons and other target cells in vivo may contribute to the resulting disease and mortality. To investigate the role of apoptosis in Sindbis virus pathogenesis, infected mouse brains were assayed by the in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling technique and for DNA ladder formation. Infection with recombinant Sindbis virus strain 633 resulted in widespread apoptosis in newborn mouse brains and spinal cords, but few apoptotic cells were observed following infection of 2-week-old animals. This finding correlates with the age-dependent mortality observed in mice. The more neurovirulent virus TE, which differs from 633 by a single amino acid in the E2 glycoprotein, induced significant apoptosis in brains and spinal cords of 2-week-old animals, consistent with its ability to cause fatal disease in older animals. Double- labeling experiments demonstrated that the apoptotic cells were also infected with Sindbis virus. Thus, Sindbis virus-induced apoptosis appears to be a direct result of virus infection and is likely to reflect pathogenic mechanisms for other viruses.

UR - http://www.scopus.com/inward/record.url?scp=0030050637&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030050637&partnerID=8YFLogxK

M3 - Article

C2 - 8627707

AN - SCOPUS:0030050637

VL - 70

SP - 1828

EP - 1835

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 3

ER -