Further studies of the RNA synthesis phenotype selected during persistent infection with vesicular stomatitis virus

Virology ◽  
1984 ◽  
Vol 136 (1) ◽  
pp. 211-220 ◽  
Author(s):  
Teryl K. Frey ◽  
Julius S. Youngner
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Persistent Infection ◽  
Rna Synthesis ◽  
Vesicular Stomatitis

scholarly journals Matrix Protein Mutations Contribute to Inefficient Induction of Apoptosis Leading to Persistent Infection of Human Neural Cells by Vesicular Stomatitis Virus

Virology ◽  
2002 ◽  
Vol 295 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Marc Desforges ◽  
Geneviève Despars ◽  
Stéphane Bérard ◽  
Myriam Gosselin ◽  
Margie O. McKenzie ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Persistent Infection ◽  
Matrix Protein ◽  
Neural Cells ◽  
Vesicular Stomatitis ◽  
Human Neural Cells ◽  
Induction Of Apoptosis ◽  
Protein Mutations

scholarly journals Opposing Effects of Inhibiting Cap Addition and Cap Methylation on Polyadenylation during Vesicular Stomatitis Virus mRNA Synthesis

2008 ◽  
Vol 83 (4) ◽  
pp. 1930-1940 ◽  
Author(s):  
Jianrong Li ◽  
Amal Rahmeh ◽  
Vesna Brusic ◽  
Sean P. J. Whelan
Keyword(s):  
Amino Acid ◽  
Vesicular Stomatitis Virus ◽  
Rna Synthesis ◽  
Full Length ◽  
Single Amino Acid ◽  
Mrna Synthesis ◽  
L Protein ◽  
Vesicular Stomatitis ◽  
Opposing Effects ◽  
Gene Junction

ABSTRACT The multifunctional large (L) polymerase protein of vesicular stomatitis virus (VSV) contains enzymatic activities essential for RNA synthesis, including mRNA cap addition and polyadenylation. We previously mapped amino acid residues G1154, T1157, H1227, and R1228, present within conserved region V (CRV) of L, as essential for mRNA cap addition. Here we show that alanine substitutions to these residues also affect 3′-end formation. Specifically, the cap-defective polymerases produced truncated transcripts that contained A-rich sequences at their 3′ termini and predominantly terminated within the first 500 nucleotides (nt) of the N gene. To examine how the cap-defective polymerases respond to an authentic VSV termination and reinitiation signal present at each gene junction, we reconstituted RNA synthesis using templates that contained genes inserted (I) at the leader-N gene junction. The I genes ranged in size from 382 to 1,098 nt and were typically transcribed into full-length uncapped transcripts. In addition to lacking a cap structure, the full-length I transcripts synthesized by the cap-defective polymerases lacked an authentic polyadenylate tail and instead contained 0 to 24 A residues. Moreover, the cap-defective polymerases were also unable to copy efficiently the downstream gene. Thus, single amino acid substitutions in CRV of L protein that inhibit cap addition also inhibit polyadenylation and sequential transcription of the genome. In contrast, an amino acid substitution, K1651A, in CRVI of L protein that completely inhibits cap methylation results in the hyperpolyadenylation of mRNA. This work reveals that inhibiting cap addition and cap methylation have opposing effects on polyadenylation during VSV mRNA synthesis and provides evidence in support of a link between correct 5′ cap formation and 3′ polyadenylation.

Conditions necessary for inhibition of protein synthesis and production of cytopathic effect in Aedes albopictus cells infected with vesicular stomatitis virus

1982 ◽  
Vol 2 (1) ◽  
pp. 66-75
Author(s):  
S Gillies ◽  
V Stollar
Keyword(s):  
Protein Synthesis ◽  
Vesicular Stomatitis Virus ◽  
Aedes Albopictus ◽  
Rna Synthesis ◽  
Cytopathic Effect ◽  
Viral Gene ◽  
Inhibition Of Protein Synthesis ◽  
Infected Cells ◽  
Vesicular Stomatitis ◽  
Aedes Albopictus Cells

The relationship between the development of cytopathic effect (CPE) and the inhibition of host macromolecular synthesis was examined in a CPE-susceptible cloned line of Aedes albopictus cells after infection with vesicular stomatitis virus. To induce rapid and maximal CPE, two conditions were required: (i) presence of serum in the medium and (ii) incubation at 34 degrees C rather than at 28 degrees C. In the absence of serum, incubation of infected cultures at 34 degrees C resulted in a significant increase in viral protein and RNA synthesis compared with that observed at 28 degrees C. However, when serum was present in the medium, by 6 h after infection protein synthesis (both host and viral) was markedly inhibited when infected cells were maintained at 34 degrees C. RNA synthesis (host and viral) was also inhibited in vesicular stomatitis virus-infected cells maintained at 34 degrees C with serum, but somewhat more slowly than protein synthesis. Examination of polysome patterns indicated that when infected cultures were maintained under conditions which predispose to CPE, more than half of the ribosomes existed as monosomes, suggesting that protein synthesis was being inhibited at the level of initiation. In addition, the phosphorylation of one (or two) polysome-associated proteins was reduced when protein synthesis was inhibited. Our findings indicate a strong correlation between virus-induced CPE in the LT-C7 clone of A. albopictus cells and the inhibition of protein synthesis. Although the mechanism of the serum effect is not understood, incubation at 34 degrees C probably predisposes to CPE and inhibition of protein synthesis by increasing the amount of viral gene products made.

scholarly journals Vesicular Stomatitis Virus Transcription Is Inhibited by TRIM69 in the Interferon-Induced Antiviral State

2019 ◽  
Vol 93 (24) ◽  
Author(s):  
Tonya Kueck ◽  
Louis-Marie Bloyet ◽  
Elena Cassella ◽  
Trinity Zang ◽  
Fabian Schmidt ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Vesicular Stomatitis Virus ◽  
Rna Synthesis ◽  
Inhibition Mechanism ◽  
Target Sequence ◽  
Messenger Rnas ◽  
Antiviral Protein ◽  
Viral Mrnas ◽  
Antiviral State ◽  
Vesicular Stomatitis

ABSTRACT Interferons (IFNs) induce the expression of interferon-stimulated genes (ISGs), many of which are responsible for the cellular antiviral state in which the replication of numerous viruses is blocked. How the majority of individual ISGs inhibit the replication of particular viruses is unknown. We conducted a loss-of-function screen to identify genes required for the activity of alpha interferon (IFN-α) against vesicular stomatitis virus, Indiana serotype (VSVIND), a prototype negative-strand RNA virus. Our screen revealed that TRIM69, a member of the tripartite motif (TRIM) family of proteins, is a VSVIND inhibitor. TRIM69 potently inhibited VSVIND replication through a previously undescribed transcriptional inhibition mechanism. Specifically, TRIM69 physically associates with the VSVIND phosphoprotein (P), requiring a specific peptide target sequence encoded therein. P is a cofactor for the viral polymerase and is required for viral RNA synthesis, as well as the assembly of replication compartments. By targeting P, TRIM69 inhibits pioneer transcription of the incoming virion-associated minus-strand RNA, thereby preventing the synthesis of viral mRNAs, and consequently impedes all downstream events in the VSVIND replication cycle. Unlike some TRIM proteins, TRIM69 does not inhibit viral replication by inducing degradation of target viral proteins. Rather, higher-order TRIM69 multimerization is required for its antiviral activity, suggesting that TRIM69 functions by sequestration or anatomical disruption of the viral machinery required for VSVIND RNA synthesis. IMPORTANCE Interferons are important antiviral cytokines that work by inducing hundreds of host genes whose products inhibit the replication of many viruses. While the antiviral activity of interferon has long been known, the identities and mechanisms of action of most interferon-induced antiviral proteins remain to be discovered. We identified gene products that are important for the antiviral activity of interferon against vesicular stomatitis virus (VSV), a model virus that whose genome consists of a single RNA molecule with negative-sense polarity. We found that a particular antiviral protein, TRIM69, functions by a previously undescribed molecular mechanism. Specifically, TRIM69 interacts with and inhibits the function of a particular phosphoprotein (P) component of the viral transcription machinery, preventing the synthesis of viral messenger RNAs.

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