Adenovirus L4-100K assembly protein is a granzyme B substrate that potently inhibits granzyme B-mediated cell death.
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.
Andrade
F
F
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Bull
H G
HG
Thornberry
N A
NA
Ketner
G W
GW
Casciola-Rosen
L A
LA
Rosen
A
A
D000260:Adenoviruses, Human / Q000378:metabolism*; D017209:Apoptosis; D001224:Aspartic Acid; D005075:Biological Evolution; D002213:Capsid / Q000378:metabolism*; D002461:Cell Line, Transformed; D053804:Granzymes; D006367:HeLa Cells; D006801:Humans; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D013379:Substrate Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015842:Serine Proteinase Inhibitors; D001224:Aspartic Acid; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases