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Journal of Virology, April 1999, p. 3125-3133, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Sendai Virus and Simian Virus 5 Block Activation of
Interferon-Responsive Genes: Importance for Virus
Pathogenesis
L.
Didcock,1
D. F.
Young,1
S.
Goodbourn,2 and
R. E.
Randall1,*
School of Biomedical Sciences, North Haugh
University of St. Andrews, Fife, Scotland KY16
9TS,1 and Department of
Biochemistry, St. George's Hospital Medical School, University of
London, London SW17 0RE, England2
Received 23 October 1998/Accepted 21 December 1998
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-
/
). However, in human cells, IFN-
/
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-
/
-responsive promoter and on that of the IFN-
promoter were examined in transient transfection experiments. The
results demonstrated that (i) SeV, but not SV5, inhibited an
IFN-
/
-responsive promoter in murine cells; (ii) both SV5 and SeV
inhibited the activation of an IFN-
/
-responsive promoter in human
cells; and (iii) in both human and murine cells, SeV was a strong
inducer of the IFN-
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.
*
Corresponding author. Mailing address: School of
Biomedical Sciences, Biomedical Sciences Bldg., North Haugh University
of St. Andrews, Fife, Scotland KY16 9TS. Phone: 44 1334 463397. Fax: 44 1334 462595. E-mail: rer{at}st-and.ac.uk.
Journal of Virology, April 1999, p. 3125-3133, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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