The Sendai virus nonstructural C proteins specifically inhibit viral mRNA synthesis

Curran, Joseph; Marq, Jean‐Baptiste; Kolakofsky, Daniel

doi:10.1016/0042-6822(92)90588-g

Cited by 147 publications

(134 citation statements)

References 28 publications

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“…SeV-C has been shown to inhibit viral RNA synthesis (7,30,46), it is known to interact with the RNA polymerase L protein (21,24), and it harbors a membrane-targeting signal (D. Garcin and D. Kolakofsky, unpublished data) that could serve to bring the nucleocapsids to the site of assembly, where M would come into play. This scenario is consistent with a clear overtranscription phenotype associated with SeV-C gene mutants (12,28,30) and with the observation that an rSeV deficient in the four C proteins was claimed to exhibit a defect in infectious virus production (28).…”

Section: Discussionsupporting

confidence: 66%

Suppression of the Sendai Virus M Protein through a Novel Short Interfering RNA Approach Inhibits Viral Particle Production but Does Not Affect Viral RNA Synthesis

Mottet-Osman

Iseni

Pelet

et al. 2007

J Virol

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Short RNA interference is more and more widely recognized as an effective method to specifically suppress viral functions in eukaryotic cells. Here, we used an experimental system that allows suppression of the Sendai virus (SeV) M protein by using a target sequence, derived from the green fluorescent protein gene, that was introduced in the 3 untranslated region of the M protein mRNA. Silencing of the M protein gene was eventually achieved by a small interfering RNA (siRNA) directed against this target sequence. This siRNA was constitutively expressed in a cell line constructed by transduction with an appropriate lentivirus vector. Suppression of the M protein was sufficient to diminish virus production by 50-to 100-fold. This level of suppression had no apparent effect on viral replication and transcription, supporting the lack of M involvement in SeV transcription or replication control.Enveloped viruses derive their envelope from cellular membranes after the viral components have assembled at the lipid bilayer. The assembly process brings together the glycoproteins spanning the lipid bilayer with the inner core of the virus particle. The inner layer of the membrane generally contains a viral protein that bridges the glycoproteins and the inner core, dubbed the matrix or M protein. M is generally considered an essential protein, without which the production of virus particle production is highly impaired if not impossible.The M protein of Sendai virus (SeV-M), a member of the Paramyxovirinae subfamily, Paramyxoviridae family, is no exception to the rule. It is synthesized in the cytoplasm and self-associates to form a leaflet at the inner face of the plasma membrane (for a recent review, see reference 45). In the virus particle, it similarly carpets the inner part of the viral envelope, interacting with the two surface glycoproteins, HN and F, on the one hand and with the viral ribonucleoprotein complex (N protein plus viral RNA) associated with the L and P proteins on the other hand (for a review, see reference 29). In addition to its role in virus particle formation, paramyxovirus M has been reported to participate in the regulation of RNA synthesis (19,27,38,40,44). Such a role for M in viral transcription control has been described for other negative-stranded RNA viruses, such as vesicular stomatitis virus (VSV) and rabies virus (both members of the Rhabdoviridae family) (9,11,26,31,49) as well as for the influenza viruses (Orthomyxovirus family) (32, 48). In addition, VSV-M has been implicated in the shutoff of cellular transcription (3, 4), and rabies virus-M has been implicated in the stimulation of viral replication in vivo (14, 15).Our laboratory has long been interested in the SeV-M protein and, in particular, in its function in virus particle formation (13,35,36,43). To perform a structure-function analysis, one would ideally like to silence expression of the resident SeV-M gene and replace it with M mutants in a search for residues or domains that can modulate its functions. One approach would con...

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Section: Discussionsupporting

confidence: 66%

Suppression of the Sendai Virus M Protein through a Novel Short Interfering RNA Approach Inhibits Viral Particle Production but Does Not Affect Viral RNA Synthesis

Mottet-Osman

Iseni

Pelet

et al. 2007

J Virol

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“…The L protein is considered to execute all of the catalytic steps of synthesis, capping and methylation of RNA (Lamb & Kolakofsky, 1996). On the other hand, the C protein has been reported to play a regulatory role, as an accessory protein, in inhibiting viral mRNA synthesis, although it is not essential for the viral RNA polymerase activity (Curran et al, 1992). Recently, we reported that the chimeric C protein with Phe at position 170 inhibited genome replication 4-fold more strongly than that with Ser in the same position (Cadd et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Isolation of an avirulent mutant of Sendai virus with two amino acid mutations from a highly virulent field strain through adaptation to LLC-MK2 cells.

Itoh

Isegawa

Hotta

et al. 1997

Journal of General Virology

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A field strain of Sendai virus (SeV) Ohita-M1 (M1) was isolated from an epidemic in an animal laboratory by passaging in mice. A mutant strain, Ohita-MVC11 (MVC11), was then obtained by passaging M1 in rhesus monkey (LLC-MK 2 ) cells. MVC11 was adapted to LLC-MK 2 cells and produced 20 times higher levels of infectious virus than M1. This increased production of infectious virus in LLC-MK 2 cells was associated with enhanced viral gene expression. However, MVC11 could not replicate efficiently in mouse lung and was not lethal to mice even when inoculated at a titre of 8i10 5 cell-

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“…Notably, in the late seventies, a regulatory role of VSV M was suggested after the analysis of RNA synthesis of temperature sensitive VSV mutants (Martinet et al, 1979;Clinton et al, 1978). It will be interesting to also include paramyxoviruses, which encode nonessential, accessory gene products able to modulate RNA synthesis, such as the RSV M2-2 (Bermingham & Collins, 1999), or the Sendai virus C proteins (Curran et al, 1992), in order to determine whether regulation of RNA synthesis by M is a general feature of nonsegmented NSVs.…”

Section: Discussionmentioning

confidence: 99%

Rabies virus matrix protein regulates the balance of virus transcription and replication

Finke

Mueller-Waldeck

Conzelmann

2003

Journal of General Virology

139

115

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RNA synthesis by negative-strand RNA viruses (NSVs) involves transcription of subgenomic mRNAs and replication of ribonucleoprotein complexes. In this study, the envelope matrix (M) protein of rabies virus (RV) was identified as a factor which inhibits transcription and stimulates replication. Transcription, but not replication, of RV minigenomes or of full-length RV was decreased by expression of heterologous M. Since RV assembly involving M and the glycoprotein G renders virus synthetically quiescent, an RV was generated with the M and G genes substituted by placeholders. Surprisingly, RNA synthesis by this recombinant was characterized not only by an increased transcription rate but also by a diminished accumulation of replication products. This phenotype was reversed in a dose-dependent manner by providing M in trans, showing that M is a replication-stimulatory factor. The role of M in determining the balance of replication and transcription was further exploited by generation of a recombinant RV with attenuated M expression, which is highly active in transcription. Regulation of RNA synthesis by matrix proteins may represent a general mechanism of nonsegmented NSVs, which is probably obscured by the silencing activity of M during virus assembly.

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The Sendai virus nonstructural C proteins specifically inhibit viral mRNA synthesis

Cited by 147 publications

References 28 publications

Suppression of the Sendai Virus M Protein through a Novel Short Interfering RNA Approach Inhibits Viral Particle Production but Does Not Affect Viral RNA Synthesis

Suppression of the Sendai Virus M Protein through a Novel Short Interfering RNA Approach Inhibits Viral Particle Production but Does Not Affect Viral RNA Synthesis

Isolation of an avirulent mutant of Sendai virus with two amino acid mutations from a highly virulent field strain through adaptation to LLC-MK2 cells.

Rabies virus matrix protein regulates the balance of virus transcription and replication

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