Imperial College London
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Prof Ed Tate

Faculty of Natural Sciences, Department of Chemistry

GSK Chair in Chemical Biology
 
 
 
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Contact

 

+44 (0)20 7594 3752e.tate Website CV

 
 
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Assistant

 

Ms Agnes Lee +44 (0)20 7594 9852

 
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Location

 

301BMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Priyamvada:2022:10.1101/2022.06.13.495866,
author = {Priyamvada, L and Kallemeijn, WW and Faronato, M and Wilkins, K and Goldsmith, CS and Cotter, CA and Ojeda, S and Solari, R and Moss, B and Tate, EW and Satheshkumar, PS},
doi = {10.1101/2022.06.13.495866},
title = {Inhibition of vaccinia virus L1 <i>N</i>-myristoylation by the host <i>N</i>-myristoyltransferase inhibitor IMP-1088 generates non-infectious virions defective in cell entry},
url = {http://dx.doi.org/10.1101/2022.06.13.495866},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>ABSTRACT</jats:title><jats:p>We have recently shown that the replication of rhinovirus, poliovirus and foot-and-mouth disease virus requires the co-translational <jats:italic>N-</jats:italic>myristoylation of viral proteins by human host cell <jats:italic>N</jats:italic>-myristoyltransferases (NMTs), and is inhibited by treatment with IMP-1088, an ultrapotent small molecule NMT inhibitor. Here, we reveal the role of <jats:italic>N</jats:italic>-myristoylation during vaccinia virus (VACV) infection in human host cells and demonstrate the anti-poxviral effects of IMP-1088. <jats:italic>N-</jats:italic>myristoylated proteins from VACV and the host were metabolically labelled with myristic acid alkyne during infection using quantitative chemical proteomics. We identified VACV proteins A16, G9 and L1 to be <jats:italic>N-</jats:italic>myristoylated. Treatment with NMT inhibitor IMP-1088 potently abrogated VACV infection, while VACV gene expression, DNA replication, morphogenesis and EV formation remained unaffected. Importantly, we observed that loss of <jats:italic>N</jats:italic>-myristoylation resulted in greatly reduced infectivity of assembled mature virus particles, characterized by significantly reduced host cell entry and a decline in membrane fusion activity of progeny virus. While the <jats:italic>N</jats:italic>-myristoylation of VACV entry proteins L1, A16 and G9 was inhibited by IMP-1088, mutational and genetic studies demonstrated that the <jats:italic>N</jats:italic>-myristoylation of L1 was the most critical for VACV entry. Given the significant genetic identity between VACV, monkeypox virus and variola virus L1 homologs, our data provides a basis for further investigating the role of <jats:italic>N</jats:italic>-myristoylation in poxviral infections as well as the potential of selective NMT inhibitors like IMP-1088 as
AU  - Priyamvada,L
AU  - Kallemeijn,WW
AU  - Faronato,M
AU  - Wilkins,K
AU  - Goldsmith,CS
AU  - Cotter,CA
AU  - Ojeda,S
AU  - Solari,R
AU  - Moss,B
AU  - Tate,EW
AU  - Satheshkumar,PS
DO  - 10.1101/2022.06.13.495866
PY  - 2022///
TI  - Inhibition of vaccinia virus L1 <i>N</i>-myristoylation by the host <i>N</i>-myristoyltransferase inhibitor IMP-1088 generates non-infectious virions defective in cell entry
UR  - http://dx.doi.org/10.1101/2022.06.13.495866
ER  -
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