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There is no doubt that viruses require cells to successfully reproduce and effectively infect the next host. The question is what is the fate of the infected cells? All eukaryotic cells can "sense" viral infections and exhibit defence strategies to oppose viral replication and spread. This often leads to the elimination of the infected cells by programmed cell death or apoptosis. This "sacrifice" of infected cells represents the most primordial response of multicellular organisms to viruses. Subverting host cell apoptosis, at least for some time, is therefore a crucial strategy of viruses to ensure their replication, the production of essential viral proteins, virus assembly and the spreading to new hosts. For that reason many viruses harbor apoptosis inhibitory genes, which once inside infected cells are expressed to circumvent apoptosis induction during the virus reproduction phase. On the other hand, viruses can take advantage of stimulating apoptosis to (i) facilitate shedding and hence dissemination, (ii) to prevent infected cells from presenting viral antigens to the immune system or (iii) to kill non-infected bystander and immune cells which would limit viral propagation. Hence the decision whether an infected host cell undergoes apoptosis or not depends on virus type and pathogenicity, its capacity to oppose antiviral responses of the infected cells and/or to evade any attack from immune cells. Viral genomes have therefore been adapted throughout evolution to satisfy the need of a particular virus to induce or inhibit apoptosis during its life cycle. Here we review the different strategies used by viruses to interfere with the two major apoptosis as well as with the innate immune signaling pathways in mammalian cells. We will focus on the intrinsic mitochondrial pathway and discuss new ideas about how particular viruses could activately engage mitochondria to induce apoptosis of their host., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The binding of ligands to death receptors elicits distinct outcomes, such as apoptosis, inflammation and necroptosis, depending on the cellular context. We have recently described that the autophagic protein TP53INP2 favors apoptosis upon death receptor signaling and is a potential biomarker of responsiveness to TRAIL treatment.

The binding of ligands to death receptors elicits distinct outcomes, such as apoptosis, inflammation and necroptosis, depending on the cellular context. We have recently described that the autophagic protein TP53INP2 favors apoptosis upon death receptor signaling and is a potential biomarker of responsiveness to TRAIL treatment. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) E2 gene disruption is one of the key features of HPV-induced cervical malignant transformation. Though it is thought to prevent progression of carcinogenesis, the pro-apoptotic function of E2 protein remains poorly understood. This study shows that expression of HPV16 E2 induces apoptosis both in HPV-positive and -negative cervical cancer cell lines and leads to hyperactivation of caspase-8 and caspase-3. Activation of these signaling factors is responsible for the observed sensitivity to apoptosis upon treatment with anti-Fas antibody or TNF-α. In addition, immunoprecipitation experiments clearly show an interaction between HPV16 E2 and c-FLIP, a key regulator of apoptotic cell death mediated by death receptor signaling. Moreover, c-FLIP and a caspase-8 inhibitor protect cells from HPV16 E2-mediated apoptosis. Overexpression of c-FLIP rescues cervical cancer cells from apoptosis induced by HPV16 E2 protein expression. The data suggest that HPV16 E2 abrogates the apoptosis-inhibitory function of c-FLIP and renders the cell hypersensitive to the Fas/FasL apoptotic signal even below threshold concentration. This suggests a novel mechanism for deregulation of cervical epithelial cell growth upon HPV-induced transformation, which is of great significance in developing therapeutic strategies for intervention of cervical carcinogenesis. [ABSTRACT FROM AUTHOR]

Background Aquaporin 1 (AQP1) is a membrane protein whose main function is to transfer water via cellular membranes. Recent studies have described important roles for AQP1 in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AQP1 in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). Methods Immunohistochemistry for the AQP1 protein was performed to investigate the expression of AQP1 in primary tumor tissues of 50 human ESCC samples underwent curative esophagectomy. Samples were categorized into two groups according to the expression of AQP1 in each of cytoplasm and nuclear membrane, and relationships with the clinicopathological features and prognosis of ESCC patients were investigated. Next, the location of AQP1 protein in TE5, TE15, and KYSE70 cells was investigated using immunofluorescence analysis. In addition, apoptosis assay was performed in these ESCC cells and the gene expression profiles of AQP1-depleted TE5 cells was analyzed using microarray and bioinformatic studies. Results In an immunohistochemical analysis, AQP1 was primarily located in the cytoplasm and/or the nuclear membrane of carcinoma cells. The 5-year survival rate of patients with the 'cytoplasm dominant' expression of AQP1 (46.8%) was significantly lower than other patients (77.6%). A multivariate analysis of the 5-year overall survival rate showed that the pT categories and cytoplasm dominance groups of AQP1 were independent prognostic factors (P = 0.042 and 0.036, respectively). Immunofluorescence analysis revealed that AQP1 protein mainly existed in the cytoplasm in TE5 and TE15 cells. On the other hand, the expression of AQP1 in KYSE170 cells was confirmed on the nuclear membrane. The depletion of AQP1 using siRNA induced apoptosis in TE5 and TE15 cells. The results of microarray analysis revealed that Death receptor signaling pathway-related genes were changed in AQP1-depleted TE5 cells. Conclusion The results of the present study suggested that the cytoplasm dominant expression of AQP1 is related to a poor prognosis in patients with ESCC, and that it regulates tumor progression by affecting Death receptor signaling pathway. These results provide insights into the role of AQP1 as a biomarker for ESCC. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]