The SH integral membrane protein of the paramyxovirus simian virus 5 is required to block apoptosis in MDBK cells

B. He, G. Y. Lin, J. E. Durbin, R. K. Durbin, R. A. Lamb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

In some cell types the paramyxovirus simian virus 5 (SV5) causes little cytopathic effect (CPE) and infection continues productively for long periods of time; e.g., SV5 can be produced from MDBK cells for up to 40 days with little CPE. SV5 differs from most paramyxoviruses in that it encodes a small (44-amino-acid) hydrophobic integral membrane protein (SH). When MDBK cells were infected with a recombinant SV5 containing a deletion of the SH gene (rSV5ΔSH), the MDBK cells exhibited an increase in CPE compared to cells infected with wild-type SV5 (recovered from cDNA; rSV5). The increased CPE correlated with an increase in apoptosis in rSV5ΔSH-infected cells over mock-infected and rSV5-infected cells when assayed for annexin V binding, DNA content (propidium iodide staining), and DNA fragmentation (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay). In rSV5ΔSH-infected MDBK cells an increase in caspase-2 and caspase-3 activities was observed. By using peptide inhibitors of individual caspases it was found that caspase-2 and caspase-3 were activated separately in rSV5ΔSH-infected cells. Expression of caspase-2 and -3 in rSV5ΔSH-infected MDBK cells appeared not to require STAT1 protein, as STAT1 protein could not be detected in SV5-infected MDBK cells. When mutant mice homologous for a targeted disruption of STAT1 were used as a model animal system and infected with the viruses it was found that rSV5ΔSH caused less mortality than wild-type rSV5, consistent with the notion of clearance of apoptotic cells in a host species.

Original languageEnglish (US)
Pages (from-to)4068-4079
Number of pages12
JournalJournal of virology
Volume75
Issue number9
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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