Article

Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine γ-Herpesvirus 68

Oregon Health and Science University, United States of America
PLoS Pathogens (Impact Factor: 8.06). 03/2008; 4(2):e25. DOI: 10.1371/journal.ppat.0040025
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ABSTRACT 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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