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Journal of Virology, March 2005, p. 3684-3691, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3684-3691.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Amsacta moorei Entomopoxvirus Inhibitor of Apoptosis Suppresses Cell Death by Binding Grim and Hid

Qianjun Li ,1,{dagger},{ddagger} Peter Liston,2,3,{dagger} Natasha Schokman,2 Jenny Mei Ho,2 and Richard W. Moyer1*

Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida,1 Children's Hospital of Eastern Ontario Research Institute,2 Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada3

Received 23 September 2004/ Accepted 3 November 2004

Inhibitor of apoptosis (iap) genes have been identified in the genomes of two independent families of insect viruses, the Baculoviridae and the Entomopoxvirinae. In this report, we examined the functional attributes of the Amsacta moorei entomopoxvirus-encoded IAP protein (AMV-IAP). The binding specificity of the individual baculoviral IAP repeat (BIR) domains of AMV-IAP was investigated by using a random-peptide, phage display library, and sequences similar to the amino termini of proapoptotic Drosophila proteins in the Reaper/Hid/Grim family were identified. Furthermore, the BIR domains of AMV-IAP protein were demonstrated to bind the mammalian IAP inhibitor Smac through the AVPI tetrapeptide sequence, suggesting that the peptide binding pocket and groove found in the insect and mammalian IAPs is conserved in this viral protein. Interaction analysis implicated BIR1 as the high-affinity site for Grim, while BIR2 interacted more strongly with Hid. Both Grim and Hid were demonstrated to interact with AMV-IAP in vivo, and Grim- or Hid-induced cell death was suppressed when AMV-IAP was coexpressed.


* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Box 100266, Gainesville, FL 32610-0266. Phone: (352) 392-7077. Fax: (352) 846-2042. E-mail: rmoyer{at}ufl.edu.

{dagger} Q.L. and P.L. contributed equally to this paper.

{ddagger} Present address: Division of Geographic Medicine, University of Alabama at Birmingham, Birmingham, AL 35294.


Journal of Virology, March 2005, p. 3684-3691, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3684-3691.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.