High level of Bcl-2 counteracts apoptosis mediated by a live rabies virus vaccine strain and induces long-term infection.
We report here that rabies virus strains, currently used to immunize wildlife against rabies, induce not only caspase-dependent apoptosis in the human lymphoblastoid Jurkat T cell line (Jurkat-vect), but also a caspase-independent pathway involving the apoptosis-inducing factor (AIF). In contrast, a strain of neurotropic RV that does not induce apoptosis did not activate caspases or induce AIF translocation. Bcl-2 overproduction in Jurkat T cells (Jurkat-Bcl-2) abolished both pathways. ERA infection and production were similar in Jurkat-vect and Jurkat-Bcl-2 cells, indicating Bcl-2 has no direct antiviral effects. Bcl-2 production is naturally upregulated by day 3 in ERA-infected Jurkat-vect cultures. The increase in Bcl-2 levels seems to be controlled by the virus infection itself and results in the establishment of long-term, persistently infected cultures that continue to produce virus. Thus, in infections with live RV vaccine strains, infected cells may be productive reservoirs of virus in the long term. This may account for the high efficacy of live rabies vaccines.
Thoulouze
Maria-Isabel
MI
NeuroImmunologie Virale, Institut Pasteur, Paris, France.
Lafage
Mireille
M
Yuste
Victor J
VJ
Baloul
Leïla
L
Edelman
Léna
L
Kroemer
Guido
G
Israel
Nicole
N
Susin
Santos A
SA
Lafon
Monique
M
D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells / Q000821:virology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011818:Rabies / Q000503:physiopathology / Q000821:virology; D011819:Rabies Vaccines; D011820:Rabies virus / Q000472:pathogenicity / Q000502:physiology*; D014613:Vaccines, Attenuated
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011819:Rabies Vaccines; D014613:Vaccines, Attenuated; D020169:Caspases