Induction of Bad-mediated apoptosis by Sindbis virus infection: involvement of pro-survival members of the Bcl-2 family.
It is known that infection with Sindbis virus (SNV) induces apoptosis, which is inhibited by two pro-survival members of the Bcl-2 family, Bcl-2 and Bcl-xL. However, the mechanism of involvement of the other members of the Bcl-2 family in SNV-induced apoptosis remains unclear. In this study we report that Bad protein, one of the pro-apoptotic Bcl-2 family members, mediates apoptosis in the mammalian cells infected with SNV. Expression of Bad was shown to promote SNV-induced apoptosis in human embryonic kidney 293T and baby hamster kidney cells. SNV infection also induced translocation of endogenous Bad into mitochondria and heterodimerization of Bad with Bcl-xL. On the other hand, the structurally most similar pro-survival members, Bcl-2, Bcl-xL, and Bcl-w, suppressed SNV-induced apoptosis in the absence of Bad, whereas Mcl-1 and A1 did not. Bcl-w could inhibit SNV-induced apoptosis in the presence of Bad, but Bcl-xL could not. Bad could be coimmunoprecipitated with Bcl-xL or Bcl-2, but not with Bcl-w. Two viral Bcl-2 homologs, E1B19K and BHRF1, also suppressed SNV-induced apoptosis irrespective of the presence of Bad and no physical association with Bad was observed. These results suggest that direct interaction of Bad with pro-survival members of the Bcl-2 family contributes to the progress of SNV-induced apoptosis and that nonbinding members restrain SNV-induced apoptosis irrespective of Bad expression.
Moriishi
Kohji
K
Research Center for Emerging Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita-shi, Osaka 565-0871, Japan. kohji@biken.osaka-u.ac.jp
Koura
Minako
M
Matsuura
Yoshiharu
Y
D018354:Alphavirus Infections / Q000821:virology*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D006367:HeLa Cells; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012845:Sindbis Virus / Q000235:genetics / Q000472:pathogenicity*; D014162:Transfection; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
C494819:BAD protein, human; C494811:BCL2L1 protein, human; D002352:Carrier Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein