Matrix Protein 2 of Influenza A Virus Blocks Autophagosome Fusion with Lysosomes

Gannagé, Monique; Dormann, Dorothee; Albrecht, Randy A.; Dengjel, Jörn; Torossi, Tania; Rämer, Patrick C.; Lee, Monica; Strowig, Till; Arrey, Frida; Conenello, Gina; Pypaert, Marc; Andersen, Jens S.; García‐Sastre, Adolfo; Münz, Christian

doi:10.1016/j.chom.2009.09.005

Cited by 457 publications

(600 citation statements)

References 60 publications

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“…Recent studies also provide evidence that HIV-1 Nef and the influenza M2 proteins interact with Beclin 1 and block autophagosome maturation. 68,69 These studies suggest that Beclin 1 complexes not only promote autophagosome formation but also maturation in different pathogens, which regulates host response in immunologic defense.…”

Section: Slammentioning

confidence: 99%

The Beclin 1 network regulates autophagy and apoptosis

et al. 2011

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Beclin 1, the mammalian orthologue of yeast Atg6, has a central role in autophagy, a process of programmed cell survival, which is increased during periods of cell stress and extinguished during the cell cycle. It interacts with several cofactors (Atg14L, UVRAG, Bif-1, Rubicon, Ambra1, HMGB1, nPIST, VMP1, SLAM, IP 3 R, PINK and survivin) to regulate the lipid kinase Vps-34 protein and promote formation of Beclin 1-Vps34-Vps15 core complexes, thereby inducing autophagy. In contrast, the BH3 domain of Beclin 1 is bound to, and inhibited by Bcl-2 or Bcl-XL. This interaction can be disrupted by phosphorylation of Bcl-2 and Beclin 1, or ubiquitination of Beclin 1. Interestingly, caspase-mediated cleavage of Beclin 1 promotes crosstalk between apoptosis and autophagy. Beclin 1 dysfunction has been implicated in many disorders, including cancer and neurodegeneration. Here, we summarize new findings regarding the organization and function of the Beclin 1 network in cellular homeostasis, focusing on the cross-regulation between apoptosis and autophagy. Cell Death and Differentiation (2011) 18, 571-580; doi:10.1038/cdd.2010 published online 11 February 2011 Autophagy is an essential process that consists of selective degradation of cellular components. There are at least three different types of autophagy described and possibly more. These autophagy types include macroautophagy (hereafter referred to as autophagy), microautophagy and chaperonemediated autophagy. 1 The initial step of autophagy is the surrounding and sequestering of cytoplasmic organelles and proteins within an isolation membrane (phagophore). Potential sources for the membrane to generate the phagophore include the Golgi complex, endosomes, the endoplasmic reticulum (ER), mitochondria and the plasma membrane. 2 The nascent membranes are fused at their edges to form double-membrane vesicles, called autophagosomes. Autophagosomes undergo a stepwise maturation process, including fusion with acidified endosomal and/or lysosomal vesicles, eventually leading to the delivery of cytoplasmic contents to lysosomal components, where they fuse, then degrade and are recycled (Figure 1a). The process of mammalian autophagy is divided into six principal steps: initiation (Figure 1b It has been well demonstrated that autophagy depends on Atg5/Atg7, is associated with microtubule-associated protein light chain 3 (LC3) truncation and lipidation, and may originate directly from the ER membrane and other membrane organelles. Furthermore, recent study has identified a Atg5/Atg7-independent pathway of autophagy. 3 This pathway of autophagy was not associated with LC3 processing but appeared to involve autophagosome formation from late endosomes and the trans-Golgi. 3 Atg7-independent autophagy had been implicated in mitochondrial clearance from reticulocytes. 4 The exact molecular basis of Atg5/Atg7-independent autophagy remains to be elucidated. Interestingly, Beclin 1 is required for Atg5/Atg7-dependent and -independent autophagy. 3 However, the presence of Beclin 1-indep...

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Section: Slammentioning

confidence: 99%

The Beclin 1 network regulates autophagy and apoptosis

et al. 2011

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“…In recent years, an increasing number of studies have demonstrated that the infection processes of morbilliviruses are closely related with autophagic flux [16,17]. However, the coxsackievirus B3, herpes simplex virus and influenza A virus have been shown to induce autophagosome formation but block the fusion of autophagosomes with lysosomes [48–50]. More importantly, MeV infection induces successive autophagic signalling, leading to a sustained increase in autophagic flux [16].…”

Section: Discussionmentioning

confidence: 99%

Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro

Yang

Xue

et al. 2018

Virulence

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Peste des petits ruminants (PPR) is an acute and highly contagious disease in small ruminants that causes significant economic losses in developing countries. An increasing number of studies have demonstrated that both autophagy and apoptosis are important cellular mechanisms for maintaining homeostasis, and they participate in the host response to pathogens. However, the crosstalk between apoptosis and autophagy in host cells during PPRV infection has not been clarified. In this study, autophagy was induced upon virus infection in caprine endometrial epithelial cells (EECs), as determined by the appearance of double- and single-membrane autophagy-like vesicles, LC3-I/LC3-II conversion, and p62 degradation. We also found that PPRV infection triggered a complete autophagic response, most likely mediated by the non-structural protein C and nucleoprotein N. Moreover, our results suggest that autophagy not only promotes the replication of PPRV in EECs but also provides a potential mechanism for inhibiting PPRV-induced apoptosis. Inhibiting autophagosome formation by wortmannin and knocking down the essential autophagic proteins Beclin-1 and ATG7 induces caspase-dependent apoptosis in EECs in PPRV infection. However, inhibiting autophagosome and lysosome fusion by NH4Cl and chloroquine did not increase the number of apoptotic cells. Collectively, these data are the first to indicate that PPRV-induced autophagy inhibits caspase-dependent apoptosis and thus contributes to the enhancement of viral replication and maturity in host cells.

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“…This benefit for HIV in blocking autophagosome degradation was only observed in macrophages, but not T cells. Similarly, a slight benefit of macroautophagy regulation for the replication of the segmented RNA virus influenza virus was observed only in canine kidney epithelial cells, but not in human lung epithelia or mouse embryonic fibroblasts [65][66] . Irrespective of a benefit for viral replication, influenza infection leads to autophagosome accumulation in a broad range of cell types 66 …”

Section: Viral Evasion From Macroautophagymentioning

confidence: 99%

MHC presentation via autophagy and how viruses escape from it

Gannagé

Münz

2010

Semin Immunopathol

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T cells detect infected and transformed cells via antigen presentation by major histocompatibility complex (MHC) molecules on the cell surface. For T cell stimulation, these MHC molecules present fragments of proteins that are expressed or taken up by the cell. These fragments are generated by distinct proteolytic mechanisms for presentation on MHC class I molecules to cytotoxic CD8(+) and on MHC class II molecules to helper CD4(+) T cells. Proteasomes are primarily involved in MHC class I ligand and lysosomes, in MHC class II ligand generation. Autophagy delivers cytoplasmic material to lysosomes and, therefore, contributes to cytoplasmic antigen presentation by MHC class II molecules. In addition, it has been recently realized that this process also supports extracellular antigen processing for MHC class II presentation and cross-presentation on MHC class I molecules. Although the exact mechanisms for the regulation of these antigen processing pathways by autophagy are still unknown, recent studies, summarized in this review, suggest that they contribute to immune responses against infections and to maintain tolerance. Moreover, they are targeted by viruses for immune escape and could maybe be harnessed for immunotherapy. These fragments are generated by distinct proteolytic mechanisms for presentation on MHC class I molecules to cytotoxic CD8 + and on MHC class II molecules to helper CD4 + T cells.Proteasomes are primarily involved in MHC class I ligand, and lysosomes in MHC class II ligand generation. Autophagy delivers cytoplasmic material to lysosomes, and, therefore, contributes to cytoplasmic antigen presentation by MHC class II molecules. In addition, it has been recently realized that this process also supports extracellular antigen processing for MHC class II presentation and cross-presentation on MHC class I molecules. Although the exact mechanisms for the regulation of these antigen processing pathways by autophagy are still unknown, recent studies, summarized in this review, suggest that they contribute to immune responses against infections and to maintain tolerance. Moreover, they are targeted by viruses for immune escape, and could maybe be harnessed for immunotherapy. Gannage and Münz 3

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Matrix Protein 2 of Influenza A Virus Blocks Autophagosome Fusion with Lysosomes

Cited by 457 publications

References 60 publications

The Beclin 1 network regulates autophagy and apoptosis

The Beclin 1 network regulates autophagy and apoptosis

Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro

MHC presentation via autophagy and how viruses escape from it

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