John Libbey Eurotext

Virologie

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Viral strategies for modulation of apoptosis Volume 5, issue 5, Septembre - Octobre 2001

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Institut Pasteur, Département sida et rétrovirus, 28, rue du Dr-Roux, 75724 Paris Cedex 15

Apoptosis is a genetically programmed suicide process which controls many biological events, including cell homeostasis, tissue morphogenesis or development of the immune system. Two main pathways are involved : 1) the death receptor pathway, represented by CD95 or TNF-Rs, which oligomerization leads to the formation of the DISC, leading to activation of caspase-8 and recruitment of effector caspases responsible for cell destruction ; 2) the mitochondrial pathway which leads to the formation of the apoptosome in response to pro-apoptotic signals, composed by the association of cytochrome c, Apaf1 and caspase-9, which will recruit caspase-3 and the cascade of effector caspases.This pathway is controled by pro-apoptotic (Bax) or anti-apoptotic (Bcl-2, Bcl-xL) members of Bcl-2 family. Numerous viral proteins interfere with these pathways because they are homologous in sequence, function, or by modulating anti- or pro-apoptotic stimuli. For example, some viruses code for v-FLIPs, which inhibit DISC formation, others code for Bcl-2 homologs which block the mitochondrial pathway, or for caspase inhibitors (CrmA, p35, IAPs) which inhibit the effector phase, others activate p53, pRB ou genes or the IFN pathway. Early cell death limits production of progeny viruses and results in stimulation of anti-viral immunity, delayed apoptosis at late stage of infection allows replication and spread of high yields of progeny viruses, inhibition of apoptosis contributes to viral latency or to cell transformation.