Structure of the poxvirus decapping enzyme D9 reveals its mechanism of cap recognition and catalysis

2021 ◽  
Author(s):  
Jessica K. Peters ◽  
Ryan W. Tibble ◽  
Marcin Warminski ◽  
Jacek Jemielity ◽  
John D. Gross
Keyword(s):  
Protein Synthesis ◽  
Active Site ◽  
Host Protein ◽  
Viral Dsrna ◽  
Viral Mrnas ◽  
Aromatic Residues ◽  
Antiviral Responses ◽  
Decapping Enzyme ◽  
Decapping Enzymes ◽  
Host Protein Synthesis

SUMMARYPoxviruses encode decapping enzymes that remove the protective 5’ cap from both host and viral mRNAs to commit transcripts for decay by the cellular exonuclease Xrn1. Decapping by these enzymes is critical for poxvirus pathogenicity by means of simultaneously suppressing host protein synthesis and limiting the accumulation of viral dsRNA, a trigger for antiviral responses. Here we present the first high resolution structural view of the vaccinia virus decapping enzyme D9. This Nudix enzyme contains a novel domain organization in which a three-helix bundle is inserted into the catalytic Nudix domain. The 5’ mRNA cap is positioned in a bipartite active site at the interface of the two domains. Specificity for the methylated guanosine cap is achieved by stacking between conserved aromatic residues in a manner similar to that observed in canonical cap binding proteins VP39, eIF4E, and CBP20 and distinct from eukaryotic decapping enzyme Dcp2.

Molecular mechanisms of virus-mediated cytopathology

1983 ◽  
Vol 303 (1114) ◽  
pp. 167-176 ◽  
Keyword(s):  
Protein Synthesis ◽  
Molecular Mechanisms ◽  
Viral Gene Expression ◽  
Nucleocytoplasmic Transport ◽  
Host Protein ◽  
Viral Gene ◽  
Animal Cells ◽  
Viral Mrnas ◽  
Protein Factor ◽  
Host Protein Synthesis

Lytic virus infections of animal cells usually lead to a variety of morphological and biochemical lesions that include inhibition of cellular macromolecular syntheses. These cytopathic effects vary in intensity for different virus-cell combinations and probably involve several overlapping mechanisms. Inhibition may be mediated by components of parental virions or require viral gene expression. In many infected cell systems the initiation of host protein synthesis is selectively blocked. This shut-off phenomenon can result from changes in membrane permeability that alter the intracellular ionic environment in favour of viral expression, successful competition of viral mRNAs for limited translational components, or a decrease in the level of cell mRNAs by inhibition of synthesis or nucleocytoplasmic transport. However, the early onset and rapidity of virus-induced inhibition, sometimes under non-permissive conditions, implies more direct mechanisms of translational inactivation. These include enhanced degradation of cellular mRNAs or specific modification of the translation apparatus in infected cells. A dramatic example of the latter occurs in poliovirus-infected HeLa cells in which intact, functional cellular mRNA persists but host protein synthesis is almost completely inhibited. The virus-induced defect is apparently related to inactivation of a protein factor that binds to the 5' end of m7G-capped mRNAs and is required for translation of host (capped) mRNAs but not for the expression of poliovirus RNA, which is not capped. This process and other possible molecular mechanisms of virus-mediated cytopathology are discussed.

scholarly journals Inhibition of Host Protein Synthesis and Degradation of Cellular mRNAs During Infection by Influenza and Herpes Simplex Virus

1982 ◽  
Vol 2 (12) ◽  
pp. 1644-1648 ◽  
Author(s):  
S. C. Inglis
Keyword(s):  
Protein Synthesis ◽  
Blot Hybridization ◽  
Host Protein ◽  
Cell Protein ◽  
Cellular Genes ◽  
Cellular Mrnas ◽  
The Stability ◽  
Simplex Virus ◽  
Host Protein Synthesis ◽  
Synthesis And Degradation

Cloned DNA copies of two cellular genes were used to monitor, by blot hybridization, the stability of particular cell mRNAs after infection by influenza virus and herpesvirus. The results indicated that the inhibition of host cell protein synthesis that accompanied infection by each virus could be explained by a reduction in the amounts of cellular mRNAs in the cytoplasm, and they suggested that this decrease was due to virus-mediated mRNA degradation.

Modification of protein synthesis initiation factors and the shut-off of host protein synthesis in adenovirus-infected cells

Virology ◽  
1989 ◽  
Vol 168 (1) ◽  
pp. 112-118 ◽  
Author(s):  
Robert P. O'Malley ◽  
Roger F. Duncan ◽  
John W.B. Hershey ◽  
Michael B. Mathews
Keyword(s):  
Protein Synthesis ◽  
Host Protein ◽  
Initiation Factors ◽  
Infected Cells ◽  
Protein Synthesis Initiation ◽  
Host Protein Synthesis

scholarly journals The dynamics of coiled bodies in the nucleus of adenovirus-infected cells.

1996 ◽  
Vol 7 (7) ◽  
pp. 1137-1151 ◽  
Author(s):  
L Rebelo ◽  
F Almeida ◽  
C Ramos ◽  
K Bohmann ◽  
A I Lamond ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Hela Cells ◽  
Host Protein ◽  
Coiled Body ◽  
Adenovirus Infection ◽  
Protein Synthesis Inhibitors ◽  
Coiled Bodies ◽  
Infected Cells ◽  
Host Protein Synthesis ◽  
Small Nuclear Ribonucleoproteins

The coiled body is a specific intranuclear structure of unknown function that is enriched in splicing small nuclear ribonucleoproteins (snRNPs). Because adenoviruses make use of the host cell-splicing machinery and subvert the normal subnuclear organization, we initially decided to investigate the effect of adenovirus infection on the coiled body. The results indicate that adenovirus infection induces the disassembly of coiled bodies and that this effect is probably secondary to the block of host protein synthesis induced by the virus. Furthermore, coiled bodies are shown to be very labile structures, with a half-life of approximately 2 h after treatment of HeLa cells with protein synthesis inhibitors. After blocking of protein synthesis, p80 coilin was detected in numerous microfoci that do not concentrate snRNP. These structures may represent precursor forms of the coiled body, which goes through a rapid cycle of assembly/disassembly in the nucleus and requires ongoing protein synthesis to reassemble.

A viral block on host protein synthesis

Science ◽  
2020 ◽  
Vol 369 (6508) ◽  
pp. 1203.4-1203
Author(s):  
Valda Vinson
Keyword(s):  
Protein Synthesis ◽  
Host Protein ◽  
Host Protein Synthesis

Peptidyl-tRNA hydrolase is involved in lambda inhibition of host protein synthesis.

1991 ◽  
Vol 10 (11) ◽  
pp. 3549-3555 ◽  
Author(s):  
M.R. García-Villegas ◽  
F.M. De La Vega ◽  
J.M. Galindo ◽  
M. Segura ◽  
R.H. Buckingham ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Host Protein ◽  
Host Protein Synthesis
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