Viral Manipulation of Cell Death

Abstract

Elucidation of the mechanisms behind cell death has brought with it an appreciation for viral strategies that target these pathways as a means to promote viral propagation while avoiding or slowing the host immune response. Several redundant anti-viral pathways have evolved in eukaryotic cells that are designed to minimize the damage due to viral infection while quickly clearing the invading pathogen. Cell death is a commonly employed immune defense against viral infection, and many viruses potently induce or suppress cell death during infection. The past decade has seen an incredible increase in our understanding of how cell death assists in host immune response, as well as how viruses have evolved to hijack or disengage these systems. By targeting components of host cell death pathways, viruses have developed the ability to control host survival and death, ensuring efficient propagation while inactivating or avoiding the immune system consequences of infection. This review focuses on the most recent and important advances in our understanding of how a wide range of viruses manipulate the survival and death of their hosts.

PA-X Decreases the Pathogenicity of Highly Pathogenic H5N1 Influenza A Virus in Avian Species by Inhibiting Virus Replication and Host Response

“…7C and 8B). Influenza virus can induce apoptosis in multiple cell types, including lymphocytes (23,24), epithelial cells (25,26), and immortalized cell lines (10,(27)(28)(29)(30); apoptosis then causes cellular and organ damage, contributing to virus pathogenicity (31)(32)(33). Thus, the accelerated cell death evoked by CK-PAX3 may be associated with the increased virulence in chickens and ducks.…”

Mitophagy switches cell death from apoptosis to necrosis in NSCLC cells treated with oncolytic measles virus

“…Apoptosis is regarded as one of the fundamental mechanisms by which hosts defend themselves against viral infection [34-36]. Since self-destruction may restrict viral replication and spread, it is plausible that MV-Edm utilizes mitophagy to counteract apoptosis and thus to favor its replication.…”

Mechanisms of apoptosis in Crustacea: what conditions induce versus suppress cell death?

“…Immune and inflammatory responses are induced by viral infection, but particularly germane for this review, successful viral replication relies on the ability of viral products to block or delay apoptosis until sufficient progeny have been produced [123]. Thus, from the perspective of the virus, the invader must escape host-induced apoptosis [124–128]. …”

“…The mechanisms known for viral evasion of apoptosis are overwhelmingly numerous and diverse [126]. In addition to encoding homologues of anti-apoptotic proteins like Bcl-2 [125] or preventing p53-mediated apoptosis [124], viruses also produce proteins like M11L, which is targeted to the mitochondrion, associates with the peripheral benzodiazepine receptor, and prevents opening of the MPTP and cyt- c release [128]. Viral mitochondrial inhibitor of apoptosis (vMIA) can form a complex with the adenine nucleotide translocator (ANT) [129], and more recently has been shown to bind to Bax and prevent Bax-dependent mitochondrial outer membrane permeabilization (MOMP) by sequestering Bax at mitochondrion as a vMIA–Bax complex [129, 130].…”