Structural Conservation and Functional Diversity of the Poxvirus Immune Evasion (PIE) Domain Superfamily

Viruses
Christopher A NelsonDaved H Fremont

Abstract

Poxviruses encode a broad array of proteins that serve to undermine host immune defenses. Structural analysis of four of these seemingly unrelated proteins revealed the recurrent use of a conserved beta-sandwich fold that has not been observed in any eukaryotic or prokaryotic protein. Herein we propose to call this unique structural scaffolding the PIE (Poxvirus Immune Evasion) domain. PIE domain containing proteins are abundant in chordopoxvirinae, with our analysis identifying 20 likely PIE subfamilies among 33 representative genomes spanning 7 genera. For example, cowpox strain Brighton Red appears to encode 10 different PIEs: vCCI, A41, C8, M2, T4 (CPVX203), and the SECRET proteins CrmB, CrmD, SCP-1, SCP-2, and SCP-3. Characterized PIE proteins all appear to be nonessential for virus replication, and all contain signal peptides for targeting to the secretory pathway. The PIE subfamilies differ primarily in the number, size, and location of structural embellishments to the beta-sandwich core that confer unique functional specificities. Reported ligands include chemokines, GM-CSF, IL-2, MHC class I, and glycosaminoglycans. We expect that the list of ligands and receptors engaged by the PIE domain will grow as we come to bette...Continue Reading

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Citations

Jul 9, 2016·The Journal of General Virology·Mark A O'DeaChris Upton
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Sep 11, 2016·Virus Genes·Chad SmithsonChris Upton
Apr 5, 2020·Journal of Clinical Medicine·Jordan R YaronAlexandra R Lucas
Aug 29, 2021·Pathogens·Francisco Javier Alvarez-de MirandaBruno Hernaez

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Methods Mentioned

BETA
SECRET
NMR
size

Software Mentioned

Phyre2
HMMER
vCCI
NetNGlyc1
Blastp
ViPR
MrBayes
ClustalX
ProtParam

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