TY - JOUR
T1 - Adenovirus L4-100K assembly protein is a Granzyme B substrate that potently inhibits Granzyme B-mediated cell death
AU - Andrade, Felipe
AU - Bull, Herbert G.
AU - Thornberry, Nancy A.
AU - Ketner, Gary W.
AU - Casciola-Rosen, Livia A.
AU - Rosen, Antony
N1 - Funding Information:
Monoclonal antibody 37–3 against DBP was generously provided by Dr. D. Brough, GenVec. The H5 ts 1 virus was a kind gift from Dr. J. Flint, Princeton University, NJ. We thank Drs. R. Siliciano and D. Nicholson for critical comments on the manuscript and H. Levitsky for helpful suggestions about cytotoxicity experiments. These studies were supported by National Institutes of Health grants AR44684 (to L.C.R.), DE12354 and HL56091 (to A.R.), the Scleroderma Research Foundation, and the SLE Foundation. A.R. is supported by a Burroughs Wellcome Fund Translational Research Award. F.A. is supported by Fulbright/Consejo Nacional de Ciencia y Tecnologia, Mexico Scholarship.
PY - 2001
Y1 - 2001
N2 - Cytotoxic lymphocytes kill virus-infected target cells and play a critical role in host recovery from viral infections. Granzyme B (GrB) is a cytotoxic lymphocyte granule protease that plays a critical role in mediating cytotoxicity. In these studies, we demonstrate that the adenovirus assembly protein L4-100K (100K) is a GrB substrate that prevents cytotoxic lymphocyte granule-induced apoptosis in infected target cells by potently inhibiting GrB. This inhibition is absolutely dependent on Asp-48 in 100K, found within a classic GrB consensus motif. 100K is the first viral protein described that exclusively targets the GrB pathway. It represents a novel class of viral protease inhibitor, in which an essential, multifunctional viral protein, which is vulnerable to specific proteolysis by GrB, expresses inhibitory function against that protease.
AB - Cytotoxic lymphocytes kill virus-infected target cells and play a critical role in host recovery from viral infections. Granzyme B (GrB) is a cytotoxic lymphocyte granule protease that plays a critical role in mediating cytotoxicity. In these studies, we demonstrate that the adenovirus assembly protein L4-100K (100K) is a GrB substrate that prevents cytotoxic lymphocyte granule-induced apoptosis in infected target cells by potently inhibiting GrB. This inhibition is absolutely dependent on Asp-48 in 100K, found within a classic GrB consensus motif. 100K is the first viral protein described that exclusively targets the GrB pathway. It represents a novel class of viral protease inhibitor, in which an essential, multifunctional viral protein, which is vulnerable to specific proteolysis by GrB, expresses inhibitory function against that protease.
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U2 - 10.1016/S1074-7613(01)00149-2
DO - 10.1016/S1074-7613(01)00149-2
M3 - Article
C2 - 11420045
AN - SCOPUS:0034954419
VL - 14
SP - 751
EP - 761
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 6
ER -