Viral inhibitors reveal overlapping themes in regulation of cell death and innate immunity

Postigo, Antonio; Ferrer, Pedro Eitz

doi:10.1016/j.micinf.2009.08.012

Cited by 20 publications

(24 citation statements)

References 44 publications

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“…These results suggest that host cell apoptosis can contribute to cell death of symbionts without prior signaling from stressed or dying symbionts. This response exhibits characteristics of a classic innate immune response, such as the removal and/or destruction of foreign bodies, so well characterized in other animals (Postigo and Ferrer, 2009;Wilson et al, 2009). A similar phenomenon has also been described in aposymbiotic larvae of the coral F. scutaria challenged with Symbiodinium sub-clade C31, which is unable to colonize this coral species (Dunn and Weis, 2009).…”

Section: Discussionmentioning

confidence: 56%

Stress and death of cnidarian host cells play a role in cnidarian bleaching

Paxton

Davy

Weis

2013

Journal of Experimental Biology

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SUMMARYCoral bleaching occurs when there is a breakdown of the symbiosis between cnidarian hosts and resident Symbiodinium spp. Multiple mechanisms for the bleaching process have been identified, including apoptosis and autophagy, and most previous work has focused on the Symbiodinium cell as the initiator of the bleaching cascade. In this work we show that it is possible for host cells to initiate apoptosis that can contribute to death of the Symbiodinium cell. First we found that colchicine, which results in apoptosis in other animals, causes cell death in the model anemone Aiptasia sp. but not in cultured Symbiodinium CCMP-830 cells or in cells freshly isolated from host Aiptasia (at least within the time frame of our study). In contrast, when symbiotic Aiptasia were incubated in colchicine, cell death in the resident Symbiodinium cells was observed, suggesting a host effect on symbiont mortality. Using live-cell confocal imaging of macerated symbiotic host cell isolates, we identified a pattern where the initiation of host cell death was followed by mortality of the resident Symbiodinium cells. This same pattern was observed in symbiotic host cells that were subjected to temperature stress. This research suggests that mortality of symbionts during temperature-induced bleaching can be initiated in part by host cell apoptosis.

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Section: Discussionmentioning

confidence: 56%

Stress and death of cnidarian host cells play a role in cnidarian bleaching

Paxton

Davy

Weis

2013

Journal of Experimental Biology

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“…Cells infected with pathogens can trigger the apoptotic pathway and cell death to prevent the pathogens from spreading (Postigo and Ferrer 2010). Such a mechanism is also used to remove damaged cells or extra cells unused in tissue formation.…”

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confidence: 99%

Inhibition of RNA Interference and Modulation of Transposable Element Expression by Cell Death in Drosophila

2011

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RNA interference (RNAi) regulates gene expression by sequence-specific destruction of RNA. It acts as a defense mechanism against viruses and represses the expression of transposable elements (TEs) and some endogenous genes. We report that mutations and transgene constructs that condition cell death suppress RNA interference in adjacent cells in Drosophila melanogaster. The reversal of RNAi is effective for both the white (w) eye color gene and green fluorescent protein (GFP), indicating the generality of the inhibition. Antiapoptotic transgenes that reverse cell death will also reverse the inhibition of RNAi. Using GFP and a low level of cell death produced by a heat shock-head involution defective (hs-hid) transgene, the inhibition appears to occur by blocking the conversion of double-stranded RNA (dsRNA) to short interfering RNA (siRNA). We also demonstrate that the mus308 gene and endogenous transposable elements, which are both regularly silenced by RNAi, are increased in expression and accompanied by a reduced level of siRNA, when cell death occurs. The finding that chronic ectopic cell death affects RNAi is critical for an understanding of the application of the technique in basic and applied studies. These results also suggest that developmental perturbations, disease states, or environmental insults that cause ectopic cell death would alter transposon and gene expression patterns in the organism by the inhibition of small RNA silencing processes.

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“…The proapoptotic Bcl-2 proteins Bak and Bax are the functionally redundant gatekeepers of this checkpoint, which is why many viruses encode inhibitors that target both proteins (19,26,30,44). Orthopoxviruses such as vaccinia virus encode F1, which was found to bind to Bak and Bim but not Bax (43,53,56).…”

Section: Discussionmentioning

confidence: 99%

“…For this reason, viruses encode a variety of proteins to prevent cell death, including inhibitors of the intrinsic pathway of apoptosis (26,44,48,52). This pathway, which is activated by a range of cellular stresses, is regulated and integrated by members of the B-cell lymphoma 2 (Bcl-2) family of proteins (61).…”

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confidence: 99%

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The Vaccinia Virus-Encoded Bcl-2 Homologues Do Not Act as Direct Bax Inhibitors

Postigo

Way

2012

J Virol

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Many viruses, including members of several poxvirus genera, encode inhibitors that block apoptosis by simultaneously binding the proapoptotic Bcl-2 proteins Bak and Bax. The Orthopoxvirus vaccinia virus encodes the Bcl-2-like F1 protein, which sequesters Bak but not Bax. However, N1, a potent virulence factor, is reported to be antiapoptotic and to interact with Bax. Here we investigated whether vaccinia virus inhibits Bak/Bax-dependent apoptosis via the cooperative action of F1 and N1. We found that Western Reserve (WR) and ⌬N1L viruses inhibited drug-and infection-induced apoptosis equally. Meanwhile, infections with ⌬F1L or ⌬N1L/F1L virus resulted in similar levels of Bax activation and apoptosis. Outside the context of infection, N1 did not block drug-or Bax-induced cell death or interact with Bax. In addition to F1 and N1, vaccinia virus encodes further structural homologs of Bcl-2 proteins that are conserved in orthopoxviruses, including A46, A52, B14, C1, C6, C16/B22, K7, and N2. However, we found that these do not associate with Bax or inhibit drug-induced cell death. Based on our findings that N1 is not an antiapoptotic protein, we propose that the F1 orthologs represent the only orthopoxvirus Bcl-2 homolog to directly inhibit the Bak/Bax checkpoint.

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Viral inhibitors reveal overlapping themes in regulation of cell death and innate immunity

Cited by 20 publications

References 44 publications

Stress and death of cnidarian host cells play a role in cnidarian bleaching

Stress and death of cnidarian host cells play a role in cnidarian bleaching

Inhibition of RNA Interference and Modulation of Transposable Element Expression by Cell Death in Drosophila

The Vaccinia Virus-Encoded Bcl-2 Homologues Do Not Act as Direct Bax Inhibitors

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