A secreted high-affinity inhibitor of human TNF from Tanapox virus.
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.
Brunetti
Craig R
CR
BioTherapeutics Group, Robarts Research Institute, 1400 Western Road, London, ON, Canada N6G 2V4.
Paulose-Murphy
Mini
M
Singh
Rajkumari
R
Qin
Jing
J
Barrett
John W
JW
Tardivel
Aubry
A
Schneider
Pascal
P
Essani
Karim
K
McFadden
Grant
G
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014999:Yaba monkey tumor virus / Q000235:genetics / Q000502:physiology; D018158:Yatapoxvirus / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D002352:Carrier Proteins; D004279:DNA, Viral; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; C069521:recombinant human tumor necrosis factor-binding protein-1