scholarly journals Targeting of the Sendai Virus C Protein to the Plasma Membrane via a Peptide-Only Membrane Anchor

2007 ◽  
Vol 81 (7) ◽  
pp. 3187-3197 ◽  
Author(s):  
Jean-Baptiste Marq ◽  
Albert Brini ◽  
Daniel Kolakofsky ◽  
Dominique Garcin
Keyword(s):  
Plasma Membrane ◽  
Sendai Virus ◽  
Intracellular Localization ◽  
Membrane Targeting ◽  
Membrane Anchor ◽  
C Protein ◽  
Cellular Antiviral Response ◽  
Α Helix ◽  
Virus C ◽  
Cellular Compartments

ABSTRACT Several cellular proteins are synthesized in the cytosol on free ribosomes and then associate with membranes due to the presence of short peptide sequences. These membrane-targeting sequences contain sites to which lipid chains are attached, which help direct the protein to a particular membrane domain and anchor it firmly in the bilayer. The intracellular concentration of these proteins in particular cellular compartments, where their interacting partners are also concentrated, is essential to their function. This paper reports that the apparently unmodified N-terminal sequence of the Sendai virus C protein (MPSFL KK IL K L R G RR . . .; letters in italics represent hydrophobic residues; underlined letters represent basic residues, which has a strong propensity to form an amphipathic α-helix in a hydrophobic environment) also function as a membrane targeting signal and membrane anchor. Moreover, the intracellular localization of the C protein at the plasma membrane is essential for inducing the interferon-independent phosphorylation of Stat1 as part of the viral program to prevent the cellular antiviral response.

scholarly journals A Short Peptide at the Amino Terminus of the Sendai Virus C Protein Acts as an Independent Element That Induces STAT1 Instability

2004 ◽  
Vol 78 (16) ◽  
pp. 8799-8811 ◽  
Author(s):  
Dominique Garcin ◽  
Jean-Baptiste Marq ◽  
Fréderic Iseni ◽  
Stephen Martin ◽  
Daniel Kolakofsky
Keyword(s):  
Protein C ◽  
Fluorescent Protein ◽  
Sendai Virus ◽  
C Protein ◽  
Protein Protein Interaction ◽  
Amino Terminal ◽  
Innate Antiviral Response ◽  
Α Helix ◽  
Virus C ◽  
Green Fluorescent

ABSTRACT The Sendai virus C protein acts to dismantle the interferon-induced cellular antiviral state in an MG132-sensitive manner, in part by inducing STAT1 instability. This activity of C maps to the first 23 amino acids (C1-23) of the 204-amino-acid (aa)-long protein (C1-204). C1-23 was found to act as an independent viral element that induces STAT1 instability, since this peptide fused to green fluorescent protein (C1-23/GFP) is at least as active as C1-204 in this respect. This peptide also induces the degradation of C1-23/GFP and other proteins to which it is fused. Most of C1-204, and particularly its amino-terminal half, is predicted to be structurally disordered. C1-23 as a peptide was found to be disordered by circular dichroism, and the first 11 aa have a strong potential to form an amphipathic α-helix in low concentrations of trifluoroethanol, which is thought to mimic protein-protein interaction. The critical degradation-determining sequence of C1-23 was mapped by mutation to eight residues near its N terminus: 4FLKKILKL11. All the large hydrophobic residues of 4FLKKILKL11, plus its ability to form an amphipathic α-helix, were found to be critical for STAT1 degradation. In contrast, C1-23/GFP self-degradation did not require 8ILKL11, nor the ability to form an α-helix throughout this region. Remarkably, C1-23/GFP also stimulated C1-204 degradation, and this degradation in trans required the same peptide determinants as for STAT1. Our results suggest that C1-204 coordinates its dual activities of regulating viral RNA synthesis and counteracting the host innate antiviral response by sensing both its own intracellular concentration and that of STAT1.

scholarly journals Recruitment of Alix/AIP1 to the plasma membrane by Sendai virus C protein facilitates budding of virus-like particles

Virology ◽  
2008 ◽  
Vol 371 (1) ◽  
pp. 108-120 ◽  
Author(s):  
Takashi Irie ◽  
Natsuko Nagata ◽  
Tetsuya Yoshida ◽  
Takemasa Sakaguchi
Keyword(s):  
Plasma Membrane ◽  
Sendai Virus ◽  
C Protein ◽  
Virus Like Particles ◽  
Virus C

scholarly journals Sendai virus C protein limits NO production in infected RAW264.7 macrophages

2018 ◽  
Vol 24 (7) ◽  
pp. 430-438 ◽  
Author(s):  
Erdenezaya Odkhuu ◽  
Takayuki Komatsu ◽  
Naoki Koide ◽  
Yoshikazu Naiki ◽  
Kenji Takeuchi ◽  
...  
Keyword(s):  
Sendai Virus ◽  
Virus Multiplication ◽  
Inos Expression ◽  
No Production ◽  
Ns1 Protein ◽  
Wild Type ◽  
C Protein ◽  
Raw264.7 Macrophages ◽  
Virus C ◽  
Stat Pathway

To suppress virus multiplication, infected macrophages produce NO. However, it remains unclear how infecting viruses then overcome NO challenge. In the present study, we report the effects of accessory protein C from Sendai virus (SeV), a prototypical paramyxovirus, on NO output. We found that in RAW264.7 murine macrophages, a mutant SeV without C protein (4C(–)) significantly enhanced inducible NO synthase (iNOS) expression and subsequent NO production compared to wild type SeV (wtSeV). SeV 4C(-) infection caused marked production of IFN-β, which is involved in induction of iNOS expression via the JAK-STAT pathway. Addition of anti-IFN-β Ab, however, resulted in only marginal suppression of NO production. In contrast, NF-κB, a primarily important factor for transcription of the iNOS gene, was also activated by 4C(–) infection but not wtSeV infection. Induction of NO production and iNOS expression by 4C(–) was significantly suppressed in cells constitutively expressing influenza virus NS1 protein that can sequester double-stranded (ds)RNA, which triggers activation of signaling pathways leading to activation of NF-κB and IRF3. Therefore, C protein appears to suppress NF-κB activation to inhibit iNOS expression and subsequent NO production, possibly by limiting dsRNA generation in the context of viral infection.

Sendai virus C protein physically associates with Stat1

2001 ◽  
Vol 6 (6) ◽  
pp. 545-557 ◽  
Author(s):  
Kenji Takeuchi ◽  
Takayuki Komatsu ◽  
Junko Yokoo ◽  
Atsushi Kato ◽  
Tatsuo Shioda ◽  
...  
Keyword(s):  
Sendai Virus ◽  
C Protein ◽  
Virus C

Sendai virus C protein impairs both phosphorylation and dephosphorylation processes of Stat1

FEBS Letters ◽  
2002 ◽  
Vol 511 (1-3) ◽  
pp. 139-144 ◽  
Author(s):  
Takayuki Komatsu ◽  
Kenji Takeuchi ◽  
Junko Yokoo ◽  
Bin Gotoh
Keyword(s):  
Sendai Virus ◽  
C Protein ◽  
Virus C

scholarly journals Dephosphorylation Failure of Tyrosine-Phosphorylated STAT1 in IFN-Stimulated Sendai Virus C Protein-Expressing Cells

Virology ◽  
2002 ◽  
Vol 293 (2) ◽  
pp. 205-209 ◽  
Author(s):  
Sakura Saito ◽  
Toshio Ogino ◽  
Naoko Miyajima ◽  
Atsushi Kato ◽  
Masayoshi Kohase
Keyword(s):  
Sendai Virus ◽  
C Protein ◽  
Virus C

Sendai virus C protein inhibits lipopolysaccharide-induced nitric oxide production through impairing interferon-β signaling

2014 ◽  
Vol 23 (1) ◽  
pp. 267-272 ◽  
Author(s):  
Erdenezaya Odkhuu ◽  
Takayuki Komatsu ◽  
Yoshikazu Naiki ◽  
Naoki Koide ◽  
Takashi Yokochi
Keyword(s):  
Nitric Oxide ◽  
Sendai Virus ◽  
Nitric Oxide Production ◽  
Interferon Β ◽  
C Protein ◽  
Oxide Production ◽  
Virus C

scholarly journals Sendai Virus C Proteins Counteract the Interferon-Mediated Induction of an Antiviral State

1999 ◽  
Vol 73 (8) ◽  
pp. 6559-6565 ◽  
Author(s):  
Dominique Garcin ◽  
Patrizia Latorre ◽  
Daniel Kolakofsky
Keyword(s):  
Sendai Virus ◽  
Antiviral Response ◽  
Single Amino Acid ◽  
Wild Type ◽  
C Protein ◽  
Antiviral State ◽  
Protein Levels ◽  
Vesicular Stomatitis ◽  
C Proteins ◽  
Virus C

ABSTRACT We have studied the relationship between the Sendai virus (SeV) C proteins (a nested set of four proteins initiated at different start codons) and the interferon (IFN)-mediated antiviral response in IFN-competent cells in culture. SeV strains containing wild-type or various mutant C proteins were examined for their ability (i) to induce an antiviral state (i.e., to prevent the growth of vesicular stomatitis virus [VSV] following a period of SeV infection), (ii) to induce the elevation of Stat1 protein levels, and (iii) to prevent IFN added concomitant with the SeV infection from inducing an antiviral state. We find that expression of the wild-type C gene and, specifically, the AUG114-initiated C protein prevents the establishment of an antiviral state: i.e., cells infected with wild-type SeV exhibited little or no increase in Stat1 levels and were permissive for VSV replication, even in the presence of exogenous IFN. In contrast, in cells infected with SeV lacking the AUG114-initiated C protein or containing a single amino acid substitution in the C protein, the level of Stat1 increased and VSV replication was inhibited. The prevention of the cellular IFN-mediated antiviral response appears to be a key determinant of SeV pathogenicity.

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