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.