Apoptosis: an innate immune response to virus infection

Everett, Helen; McFadden, Grant

doi:10.1016/s0966-842x(99)01487-0

Cited by 382 publications

(263 citation statements)

References 56 publications

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“…Thus no attempt was made in the present study to repeat the search for enteroviral RNA by in situ hybridisation or RT-PCR. Rather, we looked at the production of another protein that is upregulated in response to enteroviral infection, PKR [30], and found a strong concordance between PKR immunopositivity and that for vp1 in the islets of both type 1 and type 2 diabetic patients. This is arguably the best evidence in the present study that detection of vp1 by the Dako antibody in beta cells is indicative of a persistent enteroviral infection.…”

Section: Discussionmentioning

confidence: 99%

The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes

et al. 2009

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Aims/hypothesis Evidence that the beta cells of human patients with type 1 diabetes can be infected with enterovirus is accumulating, but it remains unclear whether such infections occur at high frequency and are important in the disease process. We have now assessed the prevalence of enteroviral capsid protein vp1 (vp1) staining in a large cohort of autopsy pancreases of recent-onset type 1 diabetic patients and a range of controls. Methods Serial sections of paraffin-embedded pancreatic autopsy samples from 72 recent-onset type 1 diabetes patients and up to 161 controls were immunostained for insulin, glucagon, vp1, double-stranded RNA activated protein kinase R (PKR) and MHC class I. Results vp1-immunopositive cells were detected in multiple islets of 44 out of 72 young recent-onset type 1 diabetic patients, compared with a total of only three islets in three out of 50 neonatal and paediatric normal controls. vp1 staining was restricted to insulin-containing beta cells. Among the control pancreases, vp1 immunopositivity was also observed in some islets from ten out of 25 type 2 diabetic patients. A strong correlation was established between islet cell vp1 positivity and PKR production in insulin-containing islets of both type 1 and type 2 diabetic patients, consistent with a persistent viral infection of the islets. Conclusions/interpretation Immunoreactive vp1 is commonly found in the islets of recent-onset type 1 diabetes patients, but only rarely in normal paediatric controls. vp1 immunostaining was also observed in some islets of type 2 diabetes patients, suggesting that the phenomenon is not restricted to type 1 diabetes patients.

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Section: Discussionmentioning

confidence: 99%

The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes

et al. 2009

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“…Programmed cell death could have arisen in unicellular organisms as a defense mechanism analogous to mammals where virus-induced apoptosis is a host defense response to block virus transmission (Everett and McFadden, 1999). However, there are no viruses known that cause acute de novo infections of S. cerevisiae to directly test this hypothesis.…”

Section: Yeast Viruses Induce Programmed Cell Deathmentioning

confidence: 99%

Mitochondrial factors with dual roles in death and survival

Berman

Ivanovska

et al. 2006

Oncogene

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At least in mammals, we have some understanding of how caspases facilitate mitochondria-mediated cell death, but the biochemical mechanisms by which other factors promote or inhibit programmed cell death are not understood. Moreover, most of these factors are only studied after treating cells with a death stimulus. A growing body of new evidence suggests that cell death regulators also have 'day jobs' in healthy cells. Even caspases, mitochondrial fission proteins and pro-death Bcl-2 family proteins appear to have normal cellular functions that promote cell survival. Here, we review some of the supporting evidence and stretch beyond the evidence to seek an understanding of the remaining questions.

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“…It is reported that the apoptosis is positively or negatively regulated when cell is infected by the various viruses (Everett & McFadden, 1999;Benedict et al, 2002). For example, gamma herpesviruses and herpes simplex viruses induce or inhibit apoptosis through the BCL-2 homologs which is key mediator of apoptotic signal transduction (Hardwick & Bellows, 2003;Sciortino et al, 2006).…”

Section: Discussionmentioning

confidence: 99%