Alternate functions of viral regulators of cell death

Yb, Chen; Sy, Seo; Dg, Kirsch; Sheu, Ting Ting; Wc, Cheng; Hardwick, J. Marie

doi:10.1038/sj.cdd.4401964

Cited by 14 publications

(14 citation statements)

References 91 publications

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“…Whereas the apoptosis of virus-infected cells may facilitate or even be required for the release of some viruses, this process generally is perceived as an altruistic antiviral response that limits virus release and the infection of surrounding cells (1,58). The effectiveness of apoptosis as an antiviral response is underlined by the existence of the many antiapoptotic strategies employed by viruses (10,89). Most viral antiapoptotic responses to date have been observed in DNA viruses.…”

mentioning

confidence: 99%

Semliki Forest Virus-Induced Endoplasmic Reticulum Stress Accelerates Apoptotic Death of Mammalian Cells

Barry

Atkinson

Ferguson

et al. 2010

J Virol

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The alphavirus Semliki Forest virus (SFV) and its derived vectors induce apoptosis in mammalian cells.Here, we show that apoptosis is associated with the loss of mitochondrial membrane potential followed by the activation of caspase-3, caspase-8, and caspase-9. Cell death can be partially suppressed by treatment with the pan-caspase inhibitor zVAD-fmk. To determine the role of SFV structural proteins in cell death, the temporal course of cell death was compared in cells infected with SFV and cells infected with SFV virus replicon particles (VRPs) lacking some or all of the virus structural genes. In the absence of virus structural proteins, cell death was delayed. The endoplasmic reticulum (ER) stress response, as determined by the splicing of X-box binding protein 1 (XBP1) transcripts and the activation of caspase-12, was activated in virus-infected cells but not in VRP (SFV lacking structural genes)-infected cells. The C/EBP-homologous protein (CHOP) was upregulated by both virus and VRP infections. The virus envelope proteins but not the virus capsid protein triggered ER stress. These results demonstrate that in NIH 3T3 cells, SFV envelope glycoproteins trigger the unfolded protein response of the ER and accelerate apoptotic cell death initiated by virus replicase activity.

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mentioning

confidence: 99%

Semliki Forest Virus-Induced Endoplasmic Reticulum Stress Accelerates Apoptotic Death of Mammalian Cells

Barry

Atkinson

Ferguson

et al. 2010

J Virol

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“…10 Some viral pro-survival proteins, such as Epstein-Barr virus BHRF1 and human herpes virus 8 vBCL-2, share structural and sequence homology with cellular Bcl-2 proteins. 11 Others, such as adenovirus E1B19K, vaccinia virus F1L, human cytomegalovirus vMIA and myxoma virus M11L, share very low or no sequence homology with Bcl-2 proteins, but are nevertheless able to directly target and inhibit Bax and Bak oligomerization.…”

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confidence: 99%

Viral pro-survival proteins block separate stages in Bax activation but changes in mitochondrial ultrastructure still occur

et al. 2008

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Mitochondrial dysfunction mediated by Bax and Bak is a critical step in mammalian cell apoptosis. However, the molecular mechanism of Bax activation remains unknown and has been difficult to investigate due to its rapid and stochastic nature. It is currently unclear whether mitochondria play a passive role in the initiation of apoptosis, remaining unaffected by cell stresses until Bax and Bak are active, or whether they actively participate in Bax/Bak activation. Here, two viral proteins, E1B19K and BHRF1, are examined for their ability to block Bax activation at different steps and thereby reveal the timing of mitochondrial changes during apoptosis. We demonstrate that BHRF1 strongly inhibits Bax activation but not upstream apoptotic signaling events, while E1B19K permits initial stages of Bax activation but prevents the subsequent oligomerization of Bax that is required for mitochondrial dysfunction. In this defined system we show that changes in mitochondrial ultrastructure, characteristic of cells undergoing apoptosis, precede Bax activation and are not blocked by E1B19K and BHRF1. We suggest that the ability of mitochondria to respond to apoptotic stress prior to Bax activation indicates that these organelles may play a direct role in activating Bax.

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“…Apoptosis is thought to be the result of innate immune processes as well as the general block in host-cell translation induced by CHIKV and other alphaviruses [47–50]. Although apoptosis was suggested to be a host-protective mechanism to limit virus production and spread, it is now recognized that the host apoptotic machinery can be hijacked by many different viruses including alphaviruses to the detriment of the host [51, 52]. The release of apoptotic blebs from dying cells has been shown to increase the spread of CHIKV from apoptotic infected cells to uninfected neighboring cells as well as macrophages in vitro [53].…”

Section: Introductionmentioning

confidence: 99%

Protective and Pathogenic Responses to Chikungunya Virus Infection

Long

Heise

2015

Curr Trop Med Rep

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Chikungunya virus (CHIKV) is an arbovirus responsible for causing epidemic outbreaks of human disease characterized by painful and often debilitating arthralgia. Recently CHIKV has moved into the Caribbean and the Americas resulting in massive outbreaks in naïve human populations. Given the importance of CHIKV as an emerging disease, a significant amount of effort has gone into interpreting the virus-host interactions that contribute to protection or virus-induced pathology following CHIKV infection, with the long term goal of using this information to develop new therapies or safe and effective anti-CHIKV vaccines. This work has made it clear that numerous distinct host responses are involved in the response to CHIKV infection, where some aspects of the host innate and adaptive immune response protect from or limit virus-induced disease, while other pathways actually exacerbate the virus-induced disease process. This review will discuss mechanisms that have been identified as playing a role in the host response to CHIKV infection and illustrate the importance of carefully evaluating these responses to determine whether they play a protective or pathologic role during CHIKV infection.

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Alternate functions of viral regulators of cell death

Cited by 14 publications

References 91 publications

Semliki Forest Virus-Induced Endoplasmic Reticulum Stress Accelerates Apoptotic Death of Mammalian Cells

Semliki Forest Virus-Induced Endoplasmic Reticulum Stress Accelerates Apoptotic Death of Mammalian Cells

Viral pro-survival proteins block separate stages in Bax activation but changes in mitochondrial ultrastructure still occur

Protective and Pathogenic Responses to Chikungunya Virus Infection

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