INHIBITION OF APOPTOSIS BY THE AFRICAN SWINE FEVER VIRUS BCL-2 HOMOLOG - ROLE OF THE BH1 DOMAIN

Citation
Y. Revilla et al., INHIBITION OF APOPTOSIS BY THE AFRICAN SWINE FEVER VIRUS BCL-2 HOMOLOG - ROLE OF THE BH1 DOMAIN, Virology, 228(2), 1997, pp. 400-404
Citations number
31
Categorie Soggetti
Virology
Journal title
ISSN journal
00426822
Volume
228
Issue
2
Year of publication
1997
Pages
400 - 404
Database
ISI
SICI code
0042-6822(1997)228:2<400:IOABTA>2.0.ZU;2-E
Abstract
The function of the African swine fever virus (ASFV) bcl-2 homologue, gene A179L, in the regulation of apoptosis was investigated using as a model system the human myeloid leukemia cell line K562 induced to die by apoptosis with inhibitors of macromolecular synthesis, a process t hat is prevented by overexpression of human bcl-2. It is shown that tr ansfection of K562 cells with the ASFV A179L gene protects these cells from apoptotic cell death induced by a combination of cycloheximide a nd actinomycin D or by treatment with cytosine arabinoside. To test th e functional role of the highly conserved BH1 domain present in the A1 79L protein, the Gly residue at position 85 was mutated to Ala, since it has been shown that substitution of the corresponding Gly in human Bcl-2 abrogates its death-repressor activity. It was found that the Gl y-to-Ala mutation in the BH1 domain of the viral protein abolished its capacity to protect the K562 cells from apoptosis, indicating that th is Gly is essential for A179L action. This finding stresses the functi onal similarity of the BH1 domains of the viral protein and cellular B cl-2. (C) 1997 Academic Press.