scholarly journals Identification of a short, highly conserved, motif required for picornavirus capsid precursor processing at distal sites

2019 ◽  
Vol 15 (1) ◽  
pp. e1007509 ◽  
Author(s):  
Thea Kristensen ◽  
Graham J. Belsham
Keyword(s):  
Precursor Processing ◽  
Conserved Motif ◽  
Capsid Precursor

scholarly journals The Cellular Chaperone Heat Shock Protein 90 Is Required for Foot-and-Mouth Disease Virus Capsid Precursor Processing and Assembly of Capsid Pentamers

2017 ◽  
Vol 92 (5) ◽  
Author(s):  
Joseph Newman ◽  
Amin S. Asfor ◽  
Stephen Berryman ◽  
Terry Jackson ◽  
Stephen Curry ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Heat Shock Protein 90 ◽  
Precursor Protein ◽  
Capsid Assembly ◽  
Precursor Processing ◽  
Capsid Precursor ◽  
Mouth Disease Virus

ABSTRACTProductive picornavirus infection requires the hijacking of host cell pathways to aid with the different stages of virus entry, synthesis of the viral polyprotein, and viral genome replication. Many picornaviruses, including foot-and-mouth disease virus (FMDV), assemble capsids via the multimerization of several copies of a single capsid precursor protein into a pentameric subunit which further encapsidates the RNA. Pentamer formation is preceded by co- and posttranslational modification of the capsid precursor (P1-2A) by viral and cellular enzymes and the subsequent rearrangement of P1-2A into a structure amenable to pentamer formation. We have developed a cell-free system to study FMDV pentamer assembly using recombinantly expressed FMDV capsid precursor and 3C protease. Using this assay, we have shown that two structurally different inhibitors of the cellular chaperone heat shock protein 90 (hsp90) impeded FMDV capsid precursor processing and subsequent pentamer formation. Treatment of FMDV permissive cells with the hsp90 inhibitor prior to infection reduced the endpoint titer by more than 10-fold while not affecting the activity of a subgenomic replicon, indicating that translation and replication of viral RNA were unaffected by the drug.IMPORTANCEFMDV of thePicornaviridaefamily is a pathogen of huge economic importance to the livestock industry due to its effect on the restriction of livestock movement and necessary control measures required following an outbreak. The study of FMDV capsid assembly, and picornavirus capsid assembly more generally, has tended to be focused upon the formation of capsids from pentameric intermediates or the immediate cotranslational modification of the capsid precursor protein. Here, we describe a system to analyze the early stages of FMDV pentameric capsid intermediate assembly and demonstrate a novel requirement for the cellular chaperone hsp90 in the formation of these pentameric intermediates. We show the added complexity involved for this process to occur, which could be the basis for a novel antiviral control mechanism for FMDV.

scholarly journals A conserved motif in human BTG1 and BTG2 proteins mediates interaction with the poly(A) binding protein PABPC1 to stimulate mRNA deadenylation

RNA Biology ◽  
2021 ◽  
pp. 1-16
Author(s):  
Hamza Amine ◽  
Nina Ripin ◽  
Sahil Sharma ◽  
Georg Stoecklin ◽  
Frédéric H Allain ◽  
...  
Keyword(s):  
Binding Protein ◽  
Conserved Motif

scholarly journals An Engineered Maturation Cleavage Provides a Recombinant Mimic of Foot-and-Mouth Disease Virus Capsid Assembly-Disassembly

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 500
Author(s):  
Joseph Newman ◽  
David J. Rowlands ◽  
Tobias J. Tuthill
Keyword(s):  
Capsid Protein ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Virion Assembly ◽  
Capsid Precursor ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Assembly Intermediate ◽  
Capsid Stability

Picornavirus capsids are assembled from 60 copies of a capsid precursor via a pentameric assembly intermediate or ‘pentamer’. Upon completion of virion assembly, a maturation event induces a final cleavage of the capsid precursor to create the capsid protein VP4, which is essential for capsid stability and entry into new cells. For the picornavirus foot-and-mouth disease virus (FMDV), intact capsids are temperature and acid-labile and can disassemble into pentamers. During disassembly, capsid protein VP4 is lost, presumably altering the structure and properties of the resulting pentamers. The purpose of this study was to compare the characteristics of recombinant “assembly” and “disassembly” pentamers. We generated recombinant versions of these different pentamers containing an engineered cleavage site to mimic the maturation cleavage. We compared the sedimentation and antigenic characteristics of these pentamers using sucrose density gradients and reactivity with an antibody panel. Pentamers mimicking the assembly pathway sedimented faster than those on the disassembly pathway suggesting that for FMDV, in common with other picornaviruses, assembly pentamers sediment at 14S whereas only pentamers on the disassembly pathway sediment at 12S. The reactivity with anti-VP4 antibodies was reduced for the 12S pentamers, consistent with the predicted loss of VP4. Reactivity with other antibodies was similar for both pentamers suggesting that major antigenic features may be preserved between the VP4 containing assembly pentamers and the disassembly pentamers lacking VP4.

scholarly journals Thyrotropin-releasing hormone (TRH) precursor processing

1989 ◽  
Vol 264 (36) ◽  
pp. 21529-21535
Author(s):  
K A Sevarino ◽  
R H Goodman ◽  
J Spiess ◽  
I M Jackson ◽  
P Wu
Keyword(s):  
Thyrotropin Releasing Hormone ◽  
Precursor Processing ◽  
Releasing Hormone
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