A Shope Fibroma virus PYRIN-only protein modulates the host immune response

Andrea Dorfleutner; Siera J. Talbott; Nicole B. Bryan; Kristin N. Funya; Stephanie L. Rellick; John C. Reed; Xianglin Shi; Yon Rojanasakul; Daniel C. Flynn; Christian Stehlik

doi:10.1007/s11262-007-0141-9

A Shope Fibroma virus PYRIN-only protein modulates the host immune response

Andrea Dorfleutner, Siera J. Talbott, Nicole B. Bryan, Kristin N. Funya, Stephanie L. Rellick, John C. Reed, Xianglin Shi, Yon Rojanasakul, Daniel C. Flynn, Christian Stehlik

Toxicology and Cancer Biology

Research output: Contribution to journal › Article › peer-review

78 Scopus citations

Abstract

PYRIN domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity to intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors to the activation of downstream effectors, including activation of Caspase-1 and NF-κB. The cellular PYD-only protein 1 (cPOP1) can block the recruitment of ASC to activated PAN receptors and thereby functions as an endogenous inhibitor of the PYD-mediated signal transduction pathway. Here we describe the identification and characterization of a Shope Fibroma homolog to cPOP1. Like cPOP1, a Shope Fibroma virus-encoded POP (vPOP), co-localizes and directly associates with ASC and inhibits PYD-mediated signal transduction. Poxviruses are known to encode immune evasive proteins to promote host cell infection and suppression of the host immune response. Poxvirus-encoded vPOPs represent a novel class of immune evasive proteins and impair the host response by blocking Cryopyrin and ASC inflammasome-mediated activation of pro-Caspase-1 and subsequent processing of pro-interleukin (IL)-1β, and expression of vPOPs causes activation of NF-κB.

Original language	English
Pages (from-to)	685-694
Number of pages	10
Journal	Virus Genes
Volume	35
Issue number	3
DOIs	https://doi.org/10.1007/s11262-007-0141-9
State	Published - Dec 2007

Bibliographical note

Funding Information:
Acknowledgments The project described was supported by Grant Number 5P20-RR-016440 (CS, DCF) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and Grant Numbers 1R21-AI-067680 (CS), 1R03-AI-067806 (CS), and R 01-AI-56324 (JCR) from NIAID/NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. We are also grateful to the support from the Alexander Bland Osborn Cancer Center Endowment (CS).

Funding

Acknowledgments The project described was supported by Grant Number 5P20-RR-016440 (CS, DCF) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and Grant Numbers 1R21-AI-067680 (CS), 1R03-AI-067806 (CS), and R 01-AI-56324 (JCR) from NIAID/NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. We are also grateful to the support from the Alexander Bland Osborn Cancer Center Endowment (CS).

Funders	Funder number
Alexander Bland Osborn Cancer Center Endowment
National Institutes of Health (NIH)	1R03-AI-067806, R 01-AI-56324
National Institute of Allergy and Infectious Diseases	R21AI067680
National Center for Research Resources

Keywords

Caspase-1
IL-1β
Inflammasome
NF-κB
PYRIN domain
Poxvirus

ASJC Scopus subject areas

Molecular Biology
Genetics
Virology

Access to Document

10.1007/s11262-007-0141-9

Cite this

@article{7930b0dc14ce4385bbf7a1ef7ded89ac,

title = "A Shope Fibroma virus PYRIN-only protein modulates the host immune response",

abstract = "PYRIN domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity to intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors to the activation of downstream effectors, including activation of Caspase-1 and NF-κB. The cellular PYD-only protein 1 (cPOP1) can block the recruitment of ASC to activated PAN receptors and thereby functions as an endogenous inhibitor of the PYD-mediated signal transduction pathway. Here we describe the identification and characterization of a Shope Fibroma homolog to cPOP1. Like cPOP1, a Shope Fibroma virus-encoded POP (vPOP), co-localizes and directly associates with ASC and inhibits PYD-mediated signal transduction. Poxviruses are known to encode immune evasive proteins to promote host cell infection and suppression of the host immune response. Poxvirus-encoded vPOPs represent a novel class of immune evasive proteins and impair the host response by blocking Cryopyrin and ASC inflammasome-mediated activation of pro-Caspase-1 and subsequent processing of pro-interleukin (IL)-1β, and expression of vPOPs causes activation of NF-κB.",

keywords = "Caspase-1, IL-1β, Inflammasome, NF-κB, PYRIN domain, Poxvirus",

author = "Andrea Dorfleutner and Talbott, {Siera J.} and Bryan, {Nicole B.} and Funya, {Kristin N.} and Rellick, {Stephanie L.} and Reed, {John C.} and Xianglin Shi and Yon Rojanasakul and Flynn, {Daniel C.} and Christian Stehlik",

note = "Funding Information: Acknowledgments The project described was supported by Grant Number 5P20-RR-016440 (CS, DCF) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and Grant Numbers 1R21-AI-067680 (CS), 1R03-AI-067806 (CS), and R 01-AI-56324 (JCR) from NIAID/NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. We are also grateful to the support from the Alexander Bland Osborn Cancer Center Endowment (CS).",

year = "2007",

month = dec,

doi = "10.1007/s11262-007-0141-9",

language = "English",

volume = "35",

pages = "685--694",

number = "3",

}

TY - JOUR

T1 - A Shope Fibroma virus PYRIN-only protein modulates the host immune response

AU - Dorfleutner, Andrea

AU - Talbott, Siera J.

AU - Bryan, Nicole B.

AU - Funya, Kristin N.

AU - Rellick, Stephanie L.

AU - Reed, John C.

AU - Shi, Xianglin

AU - Rojanasakul, Yon

AU - Flynn, Daniel C.

AU - Stehlik, Christian

N1 - Funding Information: Acknowledgments The project described was supported by Grant Number 5P20-RR-016440 (CS, DCF) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and Grant Numbers 1R21-AI-067680 (CS), 1R03-AI-067806 (CS), and R 01-AI-56324 (JCR) from NIAID/NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. We are also grateful to the support from the Alexander Bland Osborn Cancer Center Endowment (CS).

PY - 2007/12

Y1 - 2007/12

N2 - PYRIN domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity to intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors to the activation of downstream effectors, including activation of Caspase-1 and NF-κB. The cellular PYD-only protein 1 (cPOP1) can block the recruitment of ASC to activated PAN receptors and thereby functions as an endogenous inhibitor of the PYD-mediated signal transduction pathway. Here we describe the identification and characterization of a Shope Fibroma homolog to cPOP1. Like cPOP1, a Shope Fibroma virus-encoded POP (vPOP), co-localizes and directly associates with ASC and inhibits PYD-mediated signal transduction. Poxviruses are known to encode immune evasive proteins to promote host cell infection and suppression of the host immune response. Poxvirus-encoded vPOPs represent a novel class of immune evasive proteins and impair the host response by blocking Cryopyrin and ASC inflammasome-mediated activation of pro-Caspase-1 and subsequent processing of pro-interleukin (IL)-1β, and expression of vPOPs causes activation of NF-κB.

AB - PYRIN domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity to intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors to the activation of downstream effectors, including activation of Caspase-1 and NF-κB. The cellular PYD-only protein 1 (cPOP1) can block the recruitment of ASC to activated PAN receptors and thereby functions as an endogenous inhibitor of the PYD-mediated signal transduction pathway. Here we describe the identification and characterization of a Shope Fibroma homolog to cPOP1. Like cPOP1, a Shope Fibroma virus-encoded POP (vPOP), co-localizes and directly associates with ASC and inhibits PYD-mediated signal transduction. Poxviruses are known to encode immune evasive proteins to promote host cell infection and suppression of the host immune response. Poxvirus-encoded vPOPs represent a novel class of immune evasive proteins and impair the host response by blocking Cryopyrin and ASC inflammasome-mediated activation of pro-Caspase-1 and subsequent processing of pro-interleukin (IL)-1β, and expression of vPOPs causes activation of NF-κB.

KW - Caspase-1

KW - IL-1β

KW - Inflammasome

KW - NF-κB

KW - PYRIN domain

KW - Poxvirus

UR - http://www.scopus.com/inward/record.url?scp=35548929476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35548929476&partnerID=8YFLogxK

U2 - 10.1007/s11262-007-0141-9

DO - 10.1007/s11262-007-0141-9

M3 - Article

C2 - 17676277

AN - SCOPUS:35548929476

SN - 0920-8569

VL - 35

SP - 685

EP - 694

JO - Virus Genes

JF - Virus Genes

IS - 3

ER -

A Shope Fibroma virus PYRIN-only protein modulates the host immune response

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this