How do viruses control mitochondria-mediated apoptosis?
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.
Institute of Molecular Medicine, Albert Ludwigs University Freiburg, Germany.
Simon
S
Neumann
Institute of Molecular Medicine, Albert Ludwigs University Freiburg, Germany.
Souhayla
S
El Maadidi
Institute of Molecular Medicine, Albert Ludwigs University Freiburg, Germany.
Laura
L
Faletti
Institute of Molecular Medicine, Albert Ludwigs University Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University Freiburg, Germany.
Florian
F
Haun
Institute of Molecular Medicine, Albert Ludwigs University Freiburg, Germany; Centre for Biological Signaling Studies (BIOSS), Albert Ludwigs University Freiburg, Germany.
Shirin
S
Labib
Institute of Molecular Medicine, Albert Ludwigs University Freiburg, Germany; International Master of Biomedical Sciences (IMBS), Albert Ludwigs University Freiburg, Germany.
Andrea
A
Schejtman
Institute of Molecular Medicine, Albert Ludwigs University Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University Freiburg, Germany; Centre for Biological Signaling Studies (BIOSS), Albert Ludwigs University Freiburg, Germany.
Ulrich
U
Maurer
Institute of Molecular Medicine, Albert Ludwigs University Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University Freiburg, Germany; Centre for Biological Signaling Studies (BIOSS), Albert Ludwigs University Freiburg, Germany. Electronic address: christoph.borner@uniklinik-freiburg.de.
Christoph
C
Borner
D017209:Apoptosis; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008928:Mitochondria / Q000378:metabolism*; D014779:Virus Replication; D014780:Viruses / Q000254:growth & development* / Q000276:immunology*
Apoptosis; Bcl-2 family; Death receptor signaling; Innate immune signaling; Intrinsic mitochondrial signaling; RNA viruses