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Journal of Virology, April 2001, p. 3802-3810, Vol. 75, No. 8
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.8.3802-3810.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Y2, the Smallest of the Sendai Virus C Proteins, Is
Fully Capable of both Counteracting the Antiviral Action of Interferons
and Inhibiting Viral RNA Synthesis
Atsushi
Kato,1,*
Yukano
Ohnishi,2
Masayoshi
Kohase,1
Sakura
Saito,1
Masato
Tashiro,1 and
Yoshiyuki
Nagai3
Department of Viral Diseases and Vaccine
Control1 and AIDS Research
Center,3 National Institute of
Infectious Diseases, Tokyo 208-0011, and Bio-oriented Technology
Research Advancement Institution, Saitama
331-8367,2 Japan
Received 3 November 2000/Accepted 10 January 2001
An open reading frame (ORF) overlapping the amino-terminal portion
of the Sendai virus (SeV) P ORF in the +1 frame produces a
nested set of carboxy-coterminal proteins, C', C, Y1, and Y2, which are
referred to collectively as the C proteins. The C proteins are
extremely versatile triple-role players; they counteract the antiviral
action of interferons (IFNs), inhibit viral RNA synthesis, and are
involved in virus assembly. In this study, we established HeLa cell
lines stably expressing the C, Y1, and Y2 proteins individually and
examined the capacities of these cells to circumvent the antiviral action of alpha/beta IFN (IFN-
/
) and IFN-
and to inhibit viral transcription. The assay protocols included monitoring of
IFN-
/
-mediated signaling by interferon-stimulated response
element-driven reporter gene expression and of the antiviral state
induced by IFN-
/
and IFN-
and measurement of reporter gene
expression from an SeV minigenome, as well as quantification of SeV
primary transcripts. When necessary, the activities measured were
carefully normalized to the expression levels of the respective C
proteins in cells. The data obtained clearly indicate that the smallest
protein, Y2, was as active as the C and Y1 proteins in both
counteracting the antiviral action of IFNs and inhibiting viral
transcription. The data further show that intracellular transexpression
of either C, Y1, or Y2 rendered HeLa cells moderately or only poorly
permissive for not only wild-type SeV but also 4C(
) SeV, which
expressed none of the four C proteins. On the basis of these findings,
the roles of SeV C proteins in the natural life cycle are discussed.
*
Corresponding author. Mailing address: Department of
Viral Diseases and Vaccine Control, National Institute of Infectious Diseases, Gakuen 4-6-7, Musahi-Murayama, Tokyo 208-0011, Japan. Phone:
81-42-561-0711, ext. 530. Fax: 81-42-567-5631. E-mail: akato{at}nih.go.jp.
Journal of Virology, April 2001, p. 3802-3810, Vol. 75, No. 8
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.8.3802-3810.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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