A secreted high-affinity inhibitor of human TNF from Tanapox virus

Craig R. Brunetti; Mini Paulose-Murphy; Rajkumari Singh; Jing Qin; John W. Barrett; Aubry Tardivel; Pascal Schneider; Karim Essani; Grant McFadden

doi:10.1073/pnas.0737244100

A secreted high-affinity inhibitor of human TNF from Tanapox virus

Craig R. Brunetti, Mini Paulose-Murphy, Rajkumari Singh, Jing Qin, John W. Barrett, Aubry Tardivel, Pascal Schneider, Karim Essani, Grant McFadden

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

58 Scopus citations

Abstract

A class of secreted poxvirus tumor necrosis factor (TN)-binding proteins has been isolated from Tanapox-infected cell supernatants. The inhibitor bound to a TN-affinity column and was identified as the product of the 2L gene. Sequence analysis of 2L family members from other yatapoxviruses and swinepox virus yielded no sequence homology to any known cellular gene. The expressed Tanapox virus 2L protein bound to human TN with high affinity (K_d = 43 pM) and exhibits an unusually slow off-rate. However, 2L is unable to bind to a wide range of human TN family members. The 2L protein can inhibit human TN from binding to TN receptors I and II as well as block TN-induced cytolysis. Thus, Tanapox virus 2L represents an inhibitor of human TN and offers a unique strategy with which to modulate TN activity.

Original language	English (US)
Pages (from-to)	4831-4836
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	100
Issue number	8
DOIs	https://doi.org/10.1073/pnas.0737244100
State	Published - Apr 15 2003
Externally published	Yes

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title = "A secreted high-affinity inhibitor of human TNF from Tanapox virus",

abstract = "A class of secreted poxvirus tumor necrosis factor (TN)-binding proteins has been isolated from Tanapox-infected cell supernatants. The inhibitor bound to a TN-affinity column and was identified as the product of the 2L gene. Sequence analysis of 2L family members from other yatapoxviruses and swinepox virus yielded no sequence homology to any known cellular gene. The expressed Tanapox virus 2L protein bound to human TN with high affinity (Kd = 43 pM) and exhibits an unusually slow off-rate. However, 2L is unable to bind to a wide range of human TN family members. The 2L protein can inhibit human TN from binding to TN receptors I and II as well as block TN-induced cytolysis. Thus, Tanapox virus 2L represents an inhibitor of human TN and offers a unique strategy with which to modulate TN activity.",

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T1 - A secreted high-affinity inhibitor of human TNF from Tanapox virus

AU - Brunetti, Craig R.

AU - Paulose-Murphy, Mini

AU - Singh, Rajkumari

AU - Qin, Jing

AU - Barrett, John W.

AU - Tardivel, Aubry

AU - Schneider, Pascal

AU - Essani, Karim

AU - McFadden, Grant

PY - 2003/4/15

Y1 - 2003/4/15

N2 - A class of secreted poxvirus tumor necrosis factor (TN)-binding proteins has been isolated from Tanapox-infected cell supernatants. The inhibitor bound to a TN-affinity column and was identified as the product of the 2L gene. Sequence analysis of 2L family members from other yatapoxviruses and swinepox virus yielded no sequence homology to any known cellular gene. The expressed Tanapox virus 2L protein bound to human TN with high affinity (Kd = 43 pM) and exhibits an unusually slow off-rate. However, 2L is unable to bind to a wide range of human TN family members. The 2L protein can inhibit human TN from binding to TN receptors I and II as well as block TN-induced cytolysis. Thus, Tanapox virus 2L represents an inhibitor of human TN and offers a unique strategy with which to modulate TN activity.

AB - A class of secreted poxvirus tumor necrosis factor (TN)-binding proteins has been isolated from Tanapox-infected cell supernatants. The inhibitor bound to a TN-affinity column and was identified as the product of the 2L gene. Sequence analysis of 2L family members from other yatapoxviruses and swinepox virus yielded no sequence homology to any known cellular gene. The expressed Tanapox virus 2L protein bound to human TN with high affinity (Kd = 43 pM) and exhibits an unusually slow off-rate. However, 2L is unable to bind to a wide range of human TN family members. The 2L protein can inhibit human TN from binding to TN receptors I and II as well as block TN-induced cytolysis. Thus, Tanapox virus 2L represents an inhibitor of human TN and offers a unique strategy with which to modulate TN activity.

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A secreted high-affinity inhibitor of human TNF from Tanapox virus

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