Downregulation of autophagy by herpesvirus Bcl-2 homologs

The critical role of the cellular autophagy pathway in viral infection and pathogenesis has become increasingly apparent. Mounting evidences suggest that viruses have developed different strategies to meticulously modulate intracellular autophagy for their own benefits,thereby either promoting efficient viral replication or facilitating viral persistence. While our understanding of these strategies is still in its incipient stage, recent advances demonstratethat gamma herpesvirus Bcl-2 homolog (vBcl-2), which protects virus-infected cells from apoptosis, also suppresses cellular autophagy pathway through its direct interaction with theautophagy protein Beclin1. Interestingly, vBcl-2 has evolved to harbor the enhanced anti-autophagic activity compared to its host counterpart, suggesting an important role of cellular autophagy in response to viral infection and virus-associated pathogenesis. Thus, adetailed study of vBcl-2-mediated regulation of autophagy signal transduction pathway may lead to a better understanding of not only how virus escapes from host innate immunity but also how autophagy regulates viral infection and environmental stresses.

[1]  V. Deretic,et al.  Unveiling the roles of autophagy in innate and adaptive immunity , 2007, Nature Reviews Immunology.

[2]  N. Mizushima,et al.  Analysis of the Role of Autophagy in Replication of Herpes Simplex Virus in Cell Culture , 2007, Journal of Virology.

[3]  K. Kirkegaard,et al.  Modification of Cellular Autophagy Protein LC3 by Poliovirus , 2007, Journal of Virology.

[4]  Guido Kroemer,et al.  Self-eating and self-killing: crosstalk between autophagy and apoptosis , 2007, Nature Reviews Molecular Cell Biology.

[5]  Larissa B. Thackray,et al.  Coronavirus Replication Does Not Require the Autophagy Gene ATG5 , 2007, Autophagy.

[6]  E. White,et al.  Why Sick Cells Produce Tumors: The Protective Role of Autophagy , 2007, Autophagy.

[7]  E. White,et al.  Autophagy suppresses tumor progression by limiting chromosomal instability. , 2007, Genes & development.

[8]  Nektarios Tavernarakis,et al.  Functional and physical interaction between Bcl‐XL and a BH3‐like domain in Beclin‐1 , 2007, The EMBO journal.

[9]  Yigong Shi,et al.  Crystal Structure of the Bcl-XL-Beclin 1 Peptide Complex , 2007, Journal of Biological Chemistry.

[10]  J. Vicencio,et al.  BH3-Only Proteins and BH3 Mimetics Induce Autophagy by Competitively Disrupting the Interaction between Beclin 1 and Bcl-2/Bcl-XL , 2007, Autophagy.

[11]  Qihua Sun,et al.  Autophagy Gene-Dependent Clearance of Apoptotic Cells during Embryonic Development , 2007, Cell.

[12]  A. Iwasaki,et al.  In Brief , 2007, Nature Reviews Immunology.

[13]  Gordon B. Mills,et al.  The energy sensing LKB1–AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis , 2007, Nature Cell Biology.

[14]  P. Codogno,et al.  Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. , 2006, The Journal of clinical investigation.

[15]  B. Oh,et al.  Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG , 2006, Nature Cell Biology.

[16]  G. McFadden,et al.  Myxoma Virus M11L Blocks Apoptosis through Inhibition of Conformational Activation of Bax at the Mitochondria , 2006, Journal of Virology.

[17]  W. Hammerschmidt,et al.  Epstein-Barr Virus Provides a New Paradigm: A Requirement for the Immediate Inhibition of Apoptosis , 2005, PLoS biology.

[18]  D. Klionsky,et al.  Autophagy: molecular machinery for self-eating , 2005, Cell Death and Differentiation.

[19]  Junying Yuan,et al.  Autophagy in cell death: an innocent convict? , 2005, The Journal of clinical investigation.

[20]  Michael D. Schneider,et al.  Bcl-2 Antiapoptotic Proteins Inhibit Beclin 1-Dependent Autophagy , 2005, Cell.

[21]  A. Petros,et al.  A Surface Groove Essential for Viral Bcl-2 Function During Chronic Infection In Vivo , 2005, PLoS pathogens.

[22]  Shengkan Jin.  p53, Autophagy and Tumor Suppression , 2005, Autophagy.

[23]  A. Levine,et al.  The coordinate regulation of the p53 and mTOR pathways in cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[24]  R. Deberardinis,et al.  Autophagy in metazoans: cell survival in the land of plenty , 2005, Nature Reviews Molecular Cell Biology.

[25]  Joo‐Hang Kim,et al.  Essential Roles of Atg5 and FADD in Autophagic Cell Death , 2005, Journal of Biological Chemistry.

[26]  K. Kirkegaard,et al.  Subversion of Cellular Autophagosomal Machinery by RNA Viruses , 2005, PLoS biology.

[27]  A. Thorburn,et al.  Selective inactivation of a Fas-associated death domain protein (FADD)-dependent apoptosis and autophagy pathway in immortal epithelial cells. , 2005, Molecular biology of the cell.

[28]  B. Levine.  Eating Oneself and Uninvited Guests Autophagy-Related Pathways in Cellular Defense , 2005, Cell.

[29]  D. Klionsky.  The molecular machinery of autophagy: unanswered questions , 2005, Journal of Cell Science.

[30]  N. Mizushima,et al.  Coronavirus Replication Complex Formation Utilizes Components of Cellular Autophagy* , 2004, Journal of Biological Chemistry.

[31]  Jayanta Debnath,et al.  Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is required for induction of autophagy during lumen formation in vitro. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[32]  E. White,et al.  Bak and Bax Function To Limit Adenovirus Replication through Apoptosis Induction , 2002, Journal of Virology.

[33]  T. Jewett,et al.  Identification of the In Vivo Role of a Viral bcl-2 , 2002, The Journal of experimental medicine.

[34]  D. Scheuner,et al.  Regulation of starvation- and virus-induced autophagy by the eIF2α kinase signaling pathway , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[35]  S. Arico,et al.  The Tumor Suppressor PTEN Positively Regulates Macroautophagy by Inhibiting the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway* , 2001, The Journal of Biological Chemistry.

[36]  G. McFadden,et al.  Viruses and apoptosis: meddling with mitochondria. , 2001, Virology.

[37]  H. Hibshoosh,et al.  Induction of autophagy and inhibition of tumorigenesis by beclin 1 , 1999, Nature.

[38]  C. Watson,et al.  Apoptosis: the germs of death , 1999, Nature Cell Biology.

[39]  P. Allen,et al.  Inhibition of autophagy abrogates tumour necrosis factor α induced apoptosis in human T‐lymphoblastic leukaemic cells , 1997, British journal of haematology.

[40]  Jacques Neefjes,et al.  Autophagy in MHC class II presentation: sampling from within. , 2007, Immunity.

[41]  P. Stevenson,et al.  Murine gammaherpesvirus 68 bcl-2 homologue contributes to latency establishment in vivo. , 2005, The Journal of general virology.