Genetic evidence for multiple functions of the matrix protein of vesicular stomatitis virus

Coulon, Patrice; Deutsch, Victor; Lafay, Florence; Martinet-Edelist, Claire; Wyers, Françoise; Herman, Ronald C.; Flamand, Anne

doi:10.1099/0022-1317-71-4-991

Cited by 48 publications

(62 citation statements)

References 31 publications

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“…The M(51R) mutant protein, originally identified in a spontaneous temperature-sensitive mutant of VSV (tsO82) (8), inactivates the ability of M protein to inhibit transport (Fig. 6A) and affects binding to ␣M (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…A spontaneous temperature-sensitive mutant of VSV (tsO82) that is defective in blocking host cell gene expression has an altered M protein in which Met-51 is changed to arginine [M(51R) protein] (6,8). Because Met-51 lies within the region of M protein containing the ␣M epitope, we tested if this residue is important for recognition by ␣M.…”

Section: C) Gst-m Protein Was Injected 2 H Prior To Injection Of Impmentioning

confidence: 99%

“…The M protein, a major structural component of the VSV virion, plays a central role both in the inhibition of host cell gene expression (5, 42) and in viral assembly (59). These two properties are genetically separable from each other (6,8,37) in that methionine 51 (Met-51) of the M protein is required for inhibition of host cell gene expression, but not for viral assembly, whereas amino acids 4 to 21 are needed for viral assembly but not for inhibition of host cell gene expression.Previously, we showed that M protein synthesized in Xenopus laevis oocytes inhibits the import of snRNPs and karyophilic proteins, as well as the export of snRNAs and mRNAs, but not tRNAs (27). Here we use a monoclonal antibody that recognizes M protein (␣M) to investigate the mechanism of this inhibition of bidirectional nuclear transport.…”

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The Matrix Protein of Vesicular Stomatitis Virus Inhibits Nucleocytoplasmic Transport When It Is in the Nucleus and Associated with Nuclear Pore Complexes

Petersen

Her

Varvel

et al. 2000

Molecular and Cellular Biology

166

184

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The matrix (M) protein of vesicular stomatitis virus (VSV) is a potent inhibitor of bidirectional nuclear transport. Here we demonstrate that inhibition occurs when M protein is in the nucleus of Xenopus laevis oocytes and that M activity is readily reversed by a monoclonal antibody (␣M). We identify a region of M protein, amino acids 51 to 59, that is required both for inhibition of transport and for efficient recognition by ␣M. When expressed in transfected HeLa cells, M protein colocalizes with nuclear pore complexes (NPCs) at the nuclear rim. Moreover, mutation of a single amino acid, methionine 51, eliminates both transport inhibition and targeting to NPCs. We propose that M protein inhibits bidirectional transport by interacting with a component of the NPC or an NPC-associated factor that participates in nucleocytoplasmic transport.Trafficking of large macromolecules (more than 50 kDa) between the nucleus and the cytoplasm occurs through nuclear pore complexes (NPCs) via signal-dependent, carrier-mediated processes (reviewed in references 39 and 54). This transport is subject to control in response to a variety of stimuli such as progression through the cell cycle, exposure to stress, and infection by viruses (reviewed in reference 39). Thus, control of nucleocytoplasmic transport is an important element in the regulation of gene expression.Much of the carrier-mediated movement through NPCs requires cargo-specific transport receptors called importins and exportins (or karyopherins), which are members of the importin ␤ superfamily of proteins (16,21,45,61). Transport receptors can bind their cargoes either directly or via specialized adapter proteins. For example, importin ␤ mediates import of proteins containing basic nuclear localization sequences and small nuclear ribonucleoproteins (snRNPs) using the adapter proteins importin ␣ (1) and snurportin (28, 43), respectively. Importin ␤ can also interact directly with import cargoes, such as cyclin B (40, 53) and certain ribosomal proteins (30). CRM1 (Exportin1) mediates the export of proteins containing leucine-rich nuclear export signals (NES) as well as unspliced viral mRNAs and pre-snRNAs that are bound to specific NEScontaining adapter proteins (14,17,51,57). Exportin-t binds directly to its RNA export cargo, tRNA (3, 33).Directionality of nuclear transport appears to be governed largely by Ran, a small GTPase that is a central component of most known nucleocytoplasmic transport pathways (reviewed in references 9 and 41). Owing to the asymmetric localization of the Ran effector proteins RanGAP (the GTPase activating protein in the cytoplasm) and RCC1 (the guanine nucleotide exchange factor in the nucleus), a steep concentration gradient of RanGTP is presumed to exist across the nuclear envelope (29). This gradient plays a pivotal role in nucleocytoplasmic transport by triggering both assembly and disassembly of receptor-cargo complexes in the appropriate subcellular compartment (60). Thus, import complexes assemble in the cytoplasm in the absence of RanG...

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Section: Discussionmentioning

confidence: 99%

Section: C) Gst-m Protein Was Injected 2 H Prior To Injection Of Impmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The Matrix Protein of Vesicular Stomatitis Virus Inhibits Nucleocytoplasmic Transport When It Is in the Nucleus and Associated with Nuclear Pore Complexes

Petersen

Her

Varvel

et al. 2000

Molecular and Cellular Biology

166

184

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“…One of these was responsible for the structural interactions between the RNP and the lipid bilayer, as well as for the regulation of viral transcription. The second domain may be responsible for the shut-off of cellular RNA synthesis and for the recognition of cellular factor(s) required for efficient RNA synthesis (Coulon et al, 1990). Lenard & Vanderoef (1990) demonstrated that the interaction of the VSV M protein with the virus bilayer lies within the first 19 amino acid residues of the N-terminal amphipathic segment.…”

Section: Discussionmentioning

confidence: 99%

Identification of the porcine paramyxovirus LPMV matrix protein gene: comparative sequence analysis with other paramyxoviruses

Berg

Sundqvist

Moreno‐López

et al. 1991

Journal of General Virology

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The complete nucleotide sequence of the gene encoding the matrix protein (M) of the porcine paramyxovirus LPMV has been determined. The gene is 1376 nucleotides long including 5' and 3' non-coding sequences with a protein-coding sequence of 1107 nucleotides. The deduced protein, containing 369 amino acids with a calculated Mr of 41657, is hydrophobic overall with a net positive charge of +17.5. Comparative sequence analysis revealed high amino acid homology to other paramyxovirus M proteins, with the highest degree of identity (46 %) with the human mumps virus. This is strong evidence that the porcine paramyxovirus LPMV is a genuine member of the paramyxovirus genus.

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Arrested spread of vesicular stomatitis virus infections in vitro depends on interferon‐mediated antiviral activity

Lam

Duca

Yin

2005

Biotech & Bioengineering

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A quantitative understanding of the innate immune response will enable its recruitment against emerging, poorly characterized, or weaponized viral pathogens. To gain insights into how the innate responses can limit viral spread, we used quantitative focal infections to study how the spread of recombinant vesicular stomatitis viruses (VSV) on baby hamster kidney (BHK) and delayed brain tumor (DBT) cell monolayers is affected by innate cellular antiviral responses. We observed that rates of infection spread correlated with one-step growth rankings for four ectopic VSV strains: N1, N2, N3, and N4. However, this correlation was lost for M51R, a recombinant VSV mutant that lacks the ability to shut-off host gene expression. In BHK cells, M51R spread at two-thirds the rate of the recombinant control virus, XK3.1, even though their one-step growth was comparable. In DBT cells, M51R infections failed to spread beyond the site of inoculation. Addition of anti-interferon antibody restored M51R spread and one-step growth to wild-type levels. Interestingly, the antibody enhanced the spread of wild-type virus but not its growth. These results suggest that while the rate of viral spread generally correlates with the rate of viral growth, the induction of cellular antiviral activities can be in some cases, the overriding factor in both spread and growth. In summary, focal infections enabled us to visualize and quantify how viral spread was inhibited by cellular antiviral activities. This study demonstrates a mechanism for quantifying how innate cellular responses can mitigate infection spread in vitro.

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Genetic evidence for multiple functions of the matrix protein of vesicular stomatitis virus

Cited by 48 publications

References 31 publications

The Matrix Protein of Vesicular Stomatitis Virus Inhibits Nucleocytoplasmic Transport When It Is in the Nucleus and Associated with Nuclear Pore Complexes

The Matrix Protein of Vesicular Stomatitis Virus Inhibits Nucleocytoplasmic Transport When It Is in the Nucleus and Associated with Nuclear Pore Complexes

Identification of the porcine paramyxovirus LPMV matrix protein gene: comparative sequence analysis with other paramyxoviruses

Arrested spread of vesicular stomatitis virus infections in vitro depends on interferon‐mediated antiviral activity

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