Viral Control of Mitochondrial Apoptosis

Abstract

Throughout the process of pathogen–host co-evolution, viruses have developed a battery of distinct strategies to overcome biochemical and immunological defenses of the host. Thus, viruses have acquired the capacity to subvert host cell apoptosis, control inflammatory responses, and evade immune reactions. Since the elimination of infected cells via programmed cell death is one of the most ancestral defense mechanisms against infection, disabling host cell apoptosis might represent an almost obligate step in the viral life cycle. Conversely, viruses may take advantage of stimulating apoptosis, either to kill uninfected cells from the immune system, or to induce the breakdown of infected cells, thereby favoring viral dissemination. Several viral polypeptides are homologs of host-derived apoptosis-regulatory proteins, such as members of the Bcl-2 family. Moreover, viral factors with no homology to host proteins specifically target key components of the apoptotic machinery. Here, we summarize the current knowledge on the viral modulation of mitochondrial apoptosis, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus.

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

“…As viruses have developed sophisticated machineries to evade apoptotic cell death and interfere with ER stress and autophagy responses for their survival, 102,103 ICD may have played an essential role in the everlasting war between viruses and their hosts. We and other groups have found that many oncolytic viruses can induce apoptotic cell death and/or necrosis in cancer cells, 9,104,105,106 supporting their immunostimulatory potential to augment antitumor efficacy (Tables 4 and 5).…”

Role of the c subunit of the FOATP synthase in mitochondrial permeability transition

“…9 Owing to its central role in cell death regulation, MOMP is involved in the pathophysiology of human diseases as diverse as cancer, ischemia and viral infections. 10,11 MOMP can either be initiated at the outer mitochondrial membrane, owing to the pore-forming activity of the proapoptotic BCL-2 family members BAX and BAK, 12 or ensue the so-called "mitochondrial permeability transition" (MPT), an abrupt increase in the permeability of the inner mitochondrial Here, we reveal the important finding that the c subunit of the F O ATP synthase is required for MPT-driven mitochondrial fragmentation and cell death triggered by cytosolic calcium overload and oxidative stress.…”

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson’s disease

“…Viruses, as obligatory parasites, have evolved highly specific means to hijack cellular pathways. To optimize the survival in their host, many viruses express factors that block or delay the death of infected cells, by acting notably at the mitochondrial level, thereby suppressing one of the most ancient antiviral mechanisms 4 . For neurotropic viruses, protecting infected neurons from excessive damage or death makes theoretical sense to facilitate viral spread and persistence, given the poor regenerative capacity of neurons.…”