Virus-induced apoptosis and host antiviral innate immunity are key issues in understanding virus-host interactions and viral pathogenesis. Coronavirus infection of mammalian cells induces apoptotic and host innate immune responses. Global gene expression profiles are determined in coronavirus-infected Vero cells by Affymetrix array, using avian coronavirus infectious bronchitis virus (IBV) as a model system, to reveal up-regulation of both pro-apoptotic B cell lymphoma-2 (BCL-2)-antagonist/killer 1 (Bak) and pro-survival myeloid cell leukemia-1 (Mcl-1). Apoptosis occurred earlier in IBV-infected cells silenced with short interfering RNA targeting Mcl-1 (siMcl-1), and was delayed in siBak cells. Up-regulation of RNA helicases from the RIG-I-like receptor (RLR) family, Melanoma differentiation-associated gene 5 (MDA5) and Retinoic-inducible gene I (RIG-I), was also observed in IBV-infected cells, leading to downstream Mitochondrial antiviral signalling (MAVS) adaptor protein activation for interferon induction in response to viral invasion. RIG-I, MDA5 and MAVS also play a part in modulating IBV-induced apoptosis. Bcl-2 family proteins, too, regulates MAVS cleavage during apoptosis, thus further establishing a link between MAVS and intrinsic apoptotic pathway activation in the mitochondria during host innate immunity induction.