Sendai virus and Simian Virus 5 block the activation of interferon-responsive genes: importance for virus pathogenesis

L Didcock, DF Young, S Goodbourn, Richard Edward Randall

Research output: Contribution to journalArticlepeer-review

139 Citations (Scopus)

Abstract

Sendai virus (SeV) is highly pathogenic for mice. In contrast, mice (including SCID mice) infected with simian virus 5 (SV5) showed no overt signs of disease. Evidence is presented that a major factor which prevented SV5 from productively infecting mice was its inability to circumvent the interferon (IFN) response in mice. Thus, in murine cells that produce and respond to IFN, SV5 protein synthesis was rapidly switched off. In marked contrast, once SeV protein synthesis began, it continued, even if the culture medium was supplemented with alpha/beta IFN (IFN-alpha/beta). However, in human cells, IFN-alpha/beta did not inhibit the replication of either SV5 or SeV once virus protein synthesis was established. To begin to address the molecular basis for these observations, the effects of SeV and SV5 infections on the activation of an IFN-alpha/beta-responsive promoter and on that of the IFN-beta promoter were examined in transient transfection experiments. The results demonstrated that (i) SeV, but not SV5, inhibited an IFN-alpha/beta-responsive promoter in murine cells; (ii) both SV5 and SeV inhibited the activation of an IFN-alpha/beta-responsive promoter in human cells; and (iii) in both human and murine cells, SeV was a strong inducer of the IFN-beta promoter, whereas SV5 was a poor inducer. The ability of SeV and SV5 to inhibit the activation of IFN-responsive genes in human cells was confirmed by RNase protection experiments. The importance of these results in terms of paramyxovirus pathogenesis is discussed.

Original languageEnglish
Pages (from-to)3125-3133
Number of pages9
JournalJournal of Virology
Volume73
Issue number4
Publication statusPublished - Apr 1999

Keywords

  • ANTIBODY-ANTIGEN COMPLEXES
  • PROTEOLYTIC ACTIVATION
  • GAMMA-INTERFERON
  • CELLS
  • PARAMYXOVIRUS
  • INFECTION
  • PROTEINS
  • MICE
  • SIMIAN-VIRUS-5
  • IDENTIFICATION

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