title: Rabies virus-induced apoptosis involves caspase-dependent and caspase-independent pathways.
abstract: Previously, it has been shown that the laboratory attenuated rabies virus CVS-B2C, but not the wild-type virus SHBRV, induces apoptosis in mice and the induction of apoptosis is mediated by viral glycoprotein. Induction of apoptosis by CVS-B2C limits the spread of the virus in the CNS. In the present study, we characterized the pathways by which CVS-B2C induces apoptosis. BSR cells were infected with CVS-B2C or SHBRV and harvested at different time points for detection of apoptosis by immunofluorescence and flow cytometry. Apoptosis was detected only in cells infected with CVS-B2C, but not SHBRV. Caspase activity and expression of several apoptotic proteins were analyzed by fluorometric assay and Western blotting. Activation of caspase-8 and -3, but not of caspase-9, was observed in CVS-B2C-infected cells. In addition, the level of expression of Apaf-1 did not change. Furthermore, PARP was cleaved confirming activation of downstream caspases. All these data suggest that CVS-B2C infection activates the extrinsic, but not the intrinsic, apoptotic pathway. In addition, AIF, a caspase-independent apoptotic protein was up-regulated and translocated from the cytoplasm to the nucleus post-infection, suggesting that apoptosis induced by CVS-B2C also involves the activation of a caspase-independent pathway.
authors.affiliation: Department of Pathology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Luciana
authors.initials: L
authors.lastname: Sarmento
authors.forename: Tesfai
authors.initials: T
authors.lastname: Tseggai
authors.forename: Vikas
authors.initials: V
authors.lastname: Dhingra
authors.forename: Zhen F
authors.initials: ZF
authors.lastname: Fu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D011818:Rabies / Q000821:virology*; D011820:Rabies virus / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D051033:Apoptosis Inducing Factor; D053477:Apoptotic Protease-Activating Factor 1; D003094:Collagen; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases