A New Inhibitor of Apoptosis from Vaccinia Virus and Eukaryotes

PLoS Pathogens

Frank J. M van Kuppeveld¹  Caroline Gubser²  Geoffrey L Smith²  Michael Hollinshead²  Xin Lu³  Daniele Bergamaschi³ 

[1] Department of Medical Microbiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands;Department of Virology, Faculty of Medicine, Imperial College London, London, United Kingdom;Ludwig Institute for Cancer Research, Faculty of Medicine, Imperial College London, London, United Kingdom

关键词: Apoptosis;    Small interfering RNAs;    Transfection;    HeLa cells;    Animal models of infection;    Fluorescence imaging;    Reverse transcriptase-polymerase chain reaction;    Viral evolution;   

DOI  :  10.1371/journal.ppat.0030017

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

A new apoptosis inhibitor is described from vaccinia virus, camelpox virus, and eukaryotic cells. The inhibitor is a hydrophobic, multiple transmembrane protein that is resident in the Golgi and is named GAAP (Golgi anti-apoptotic protein). Stable expression of both viral GAAP (v-GAAP) and human GAAP (h-GAAP), which is expressed in all human tissues tested, inhibited apoptosis induced by intrinsic and extrinsic apoptotic stimuli. Conversely, knockout of h-GAAP by siRNA induced cell death by apoptosis. v-GAAP and h-GAAP display overlapping functions as shown by the ability of v-GAAP to complement for the loss of h-GAAP. Lastly, deletion of the v-GAAP gene from vaccinia virus did not affect virus replication in cell culture, but affected virus virulence in a murine infection model. This study identifies a new regulator of cell death that is highly conserved in evolution from plants to insects, amphibians, mammals, and poxviruses.

【 授权许可】

CC BY