Ku B, Woo JS, Liang C, Lee KH, Hong HS, E X et al.. Structural and biochemical bases for the inhibition of autophagy and apoptosis by viral BCL-2 of murine gamma-herpesvirus 68. PLoS Pathog 4: e25

Oregon Health and Science University, United States of America
PLoS Pathogens (Impact Factor: 7.56). 03/2008; 4(2):e25. DOI: 10.1371/journal.ppat.0040025
Source: PubMed


Author Summary

In higher animals, defective or surplus cells are removed by a process known as apoptosis. On the other hand, defective or damaged cellular components are removed by a process known as autophagy. These two destructive processes are indispensable for the survival and development of an organism. While apoptosis is known as a central host defense mechanism that removes virus-infected cells, the role of autophagy against viral infection has recently emerged. Many viruses express an armory of viral proteins that counteract cell death–mediated innate immune control. One such protein is a homologue of the cellular BCL-2 protein that suppresses apoptosis through inhibitory binding to apoptosis-promoting proteins. Murine γ-herpesvirus 68 also encodes a viral BCL-2, known as M11. In this study, we quantitatively measured the binding affinity of M11 for its potential cellular targets, including ten different proapoptotic proteins and the proautophagic protein Beclin1. We found that M11 neutralizes the proapoptotic proteins broadly rather than selectively to suppress apoptosis. Surprisingly, M11 bound to Beclin1 with the highest affinity, which correlated with its strong antiautophagic activity in cells. These data suggest that M11 suppresses not only apoptosis but also autophagy potently, which ultimately contributes to the viral chronic infection.

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Available from: Xiaofei Ee, Jun 19, 2014
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    • "ICP34.5 binding to Beclin 1 inhibits the formation of autophagosomes in neurons, suggesting that the virus has evolved to actively inhibit autophagy. Other viral proteins inhibiting through Beclin 1 binding include Bcl-2 homologs, such as the KSHV orf16 protein and the MHV-68 M11 protein (Ku et al., 2008; Su et al., 2014). In addition to ICP34.5's "
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    ABSTRACT: Studies of the cellular autophagy pathway have exploded over the past twenty years. Now appreciated as a constitutive degradative mechanism that promotes cellular homeostasis, autophagy is also required for a variety of developmental processes, cellular stress responses, and immune pathways. Autophagy certainly acts as both an anti-viral and pro-viral pathway, and the roles of autophagy depend on the virus, the cell type, and the cellular environment. The goal of this review is to summarize, in brief, what we know so far about the relationship between autophagy and viruses, particularly for those who are not familiar with the field. With a massive amount of relevant published data, it is simply not possible to be comprehensive, or to provide a complete "parade of viruses", and apologies are offered to researchers whose work is not described herein. Rather, this review is organized around general themes regarding the relationship between autophagy and animal viruses. Copyright © 2015. Published by Elsevier Inc.
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    • "However, the utilization of autophagic membranes has not been reported so far for DNA viruses. Indeed, herpes viruses rather seem to encode Bcl-2 homologues that inhibit autophagosome formation via their binding to Atg6/Beclin-1 (E et al., 2009; Ku et al., 2008; Orvedahl et al., 2007; Pattingre et al., 2005 "
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    12/2014; 1(2-3):116-125. DOI:10.1016/j.ebiom.2014.11.007
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    • "B. Autophagy inhibition by interfering with autophagosome formation Kaposi Sarcoma Herpes Virus vFLIP target Beclin-1 [34] Murine Gamma Herpes Virus 68 M11 encode viral Bcl 2 homolog [35] Herpes Simplex Virus 1 ICP34.5 encode viral Bcl 2 homolog [36] by interfering with autophagosome maturation or degradation HIV 1 Nef interact with Beclin-1 [37] Influenza A virus Matrix (M2) interact with Beclin-1 [38] by autolysosomal degradation Coxsackie Virus B3 e e [39] "
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