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
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.