Viral homologs of BCL-2: role of apoptosis in the regulation of virus infection

Cellular BCL-2-related proteins (cBCL-2s) function as regulators of programmed cell death (apoptosis), in part by modulating the release of proapoptotic signaling molecules from mitochondria. These factors act to promote activation of cysteine proteases of the caspase family and thereby propagate si...

Full description

Saved in:
Bibliographic Details
Published in:Genes & development 2002-10, Vol.16 (19), p.2465-2478
Main Authors: Cuconati, Andrea, White, Eileen
Format: Article
Language:English
Subjects:
Adenoviridae - metabolism
Adenoviridae - physiology
Adenovirus E1B Proteins - metabolism
Adenovirus E1B Proteins - physiology
Amino Acid Sequence
Animals
Antiviral Agents
Apoptosis
Apoptosis Regulatory Proteins
bcl-2 Homologous Antagonist-Killer Protein
bcl-2-Associated X Protein
Fas Ligand Protein
Herpesviridae - metabolism
Herpesviridae - physiology
Humans
Membrane Glycoproteins - metabolism
Membrane Proteins - metabolism
Membrane Proteins - physiology
Molecular Sequence Data
Oncogene Proteins
Poxviridae - metabolism
Poxviridae - physiology
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins - physiology
Proto-Oncogene Proteins c-bcl-2 - metabolism
Proto-Oncogene Proteins c-bcl-2 - physiology
Sequence Homology, Amino Acid
Signal Transduction
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha - metabolism
Viral Proteins - metabolism
Viral Proteins - physiology
Virus Latency
Virus Replication
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cellular BCL-2-related proteins (cBCL-2s) function as regulators of programmed cell death (apoptosis), in part by modulating the release of proapoptotic signaling molecules from mitochondria. These factors act to promote activation of cysteine proteases of the caspase family and thereby propagate signaling of apoptotic cell death. DNA viruses are known to encode homologs of cellular anti-apoptotic BCL-2 proteins (vBCL-2s), and the role of vBCL-2s in various aspects of viral infection and the mechanism by which they function have been gradually emerging. It is now apparent that inhibition of apoptosis by vBCL-2s in infected cells can prevent premature death of the host cell, which would impair virus production; can enable efficient emergence from latency; can facilitate persistent infection; and contributes to the avoidance of immune surveillance by the host. Thus, apoptosis is clearly a mechanism used by the host immune system and the infected host cell itself as part of the antiviral response. Deregulation of this delicate host-pathogen interaction can alter the course of virus replication, which may explain aspects of viral disease. Recent evidence suggests that vBCL-2s may target the core cellular proapoptotic machinery for inhibition, perhaps to secure a broad spectrum of apoptosis inhibition to the infected cell. Furthermore, because vBCL-2 family members and some of their cellular counterparts are oncogenic, deciphering their mode of action may be useful in understanding and thwarting human cancer. In this review we outline the role and the mechanism of action of vBCL-2 proteins in infected cells and how and why their function may be distinct from some of their cellular homologs.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.1012702