Activation of caspases and p53 by bovine herpesvirus 1 infection results in programmed cell death and efficient virus release

Laxminarayana R. Devireddy, Clinton J. Jones

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Programmed cell death (PCD), or apoptosis, is initiated in response to various stimuli, including virus infection. Bovine herpesvirus 1 (BHV-1) induces PCD in peripheral blood mononuclear cells at the G0/G1 phase of the cell cycle (E. Hanon, S. Hoornaert, F. Dequiedt, A. Vanderplasschen, J. Lyaku, L. Willems, and P.-P. Pastoret, Virology 232:351-358, 1997). However, penetration of virus particles is not required for PCD (E. Hanon, G. Meyer, A. Vanderplasschen, C. Dessy-Doize, E. Thiry, and P. P. Pastoret, J. Virol. 72:7638-7641, 1998). The mechanism by which BHV-1 induces PCD in peripheral blood mononuclear cells is not understood, nor is it clear whether nonlymphoid cells undergo PCD following infection. This study demonstrates that infection of bovine kidney (MDBK) cells with BHV-1 leads to PCD, as judged by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, DNA laddering, and chromatin condensation, p53 appears to be important in this process, because p53 levels and promoter activity increased after infection. Expression of proteins that are stimulated by p53 (p21(Waf1) and Bax) is also activated after infection. Cleavage of Bcl-x(L), a protein that inhibits PCD, occurred after infection, suggesting that caspases (interleukin-1β-converting enzyme-like proteases) were activated. Other caspase substrates [poly(ADP-ribose) polymerase and actin] are also cleaved during the late stages of infection. Inhibition of caspase activity delayed cytotoxic activity and virus release but increased the overall virus yield. Taken together, these results indicate that nonlymphoid cells undergo PCD near the end of productive infection and further suggest that caspases enhance virus release.

Original languageEnglish (US)
Pages (from-to)3778-3788
Number of pages11
JournalJournal of virology
Volume73
Issue number5
StatePublished - May 3 1999

Fingerprint

Bovine Herpesvirus 1
Virus Release
Herpesviridae Infections
Bovine herpesvirus 1
caspases
Caspases
Cell Death
apoptosis
viruses
Infection
infection
Caspase 1
Blood Cells
mononuclear leukocytes
Cell Cycle Resting Phase
Virology
Apoptosis Regulatory Proteins
DNA Nucleotidylexotransferase
Poly(ADP-ribose) Polymerases
G1 Phase

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Activation of caspases and p53 by bovine herpesvirus 1 infection results in programmed cell death and efficient virus release. / Devireddy, Laxminarayana R.; Jones, Clinton J.

In: Journal of virology, Vol. 73, No. 5, 03.05.1999, p. 3778-3788.

Research output: Contribution to journalArticle

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