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

被引：47

作者：

Brunetti, CR

Paulose-Murphy, M

Singh, R

Qin, J

Barrett, JW

Tardivel, A

Schneider, P

Essani, K

McFadden, G

机构：

[1] Robarts Res Inst, BioTherapeut Grp, London, ON N6G 2V4, Canada

[2] Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 5C1, Canada

[3] Univ Lausanne, BIL Biomed Res Ctr, Inst Biochem, CH-1066 Epalinges, Switzerland

[4] Western Michigan Univ, Dept Biol Sci, Virol Lab, Kalamazoo, MI 49008 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2003年 / 100卷 / 08期

关键词：

D O I：

10.1073/pnas.0737244100

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A class of secreted poxvirus tumor necrosis factor (TNF)-binding proteins has been isolated from Tanapox-infected cell supernatants. The inhibitor bound to a TNF-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 TNF 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 TNF family members. The 2L protein can inhibit human TNF from binding to TNF receptors I and II as well as block TNF-induced cytolysis. Thus, Tanapox virus 2L represents an inhibitor of human TNF and offers a unique strategy with which to modulate TNF activity.

引用

页码：4831 / 4836

页数：6

共 33 条

[31] MYXOMA VIRUS EXPRESSES A SECRETED PROTEIN WITH HOMOLOGY TO THE TUMOR-NECROSIS-FACTOR RECEPTOR GENE FAMILY THAT CONTRIBUTES TO VIRAL VIRULENCE [J].