Adenovirus L4-100K assembly protein is a Granzyme B substrate that potently inhibits Granzyme B-mediated cell death

Felipe Andrade, Herbert G. Bull, Nancy A. Thornberry, Gary W. Ketner, Livia A. Casciola-Rosen, Antony Rosen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)751-761
Number of pages11
JournalImmunity
Volume14
Issue number6
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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