Rabies virus infects mouse and human lymphocytes and induces apoptosis.
Attenuated and highly neurovirulent rabies virus strains have distinct cellular tropisms. Highly neurovirulent strains such as the challenge virus standard (CVS) are highly neurotropic, whereas the attenuated strain ERA also infects nonneuronal cells. We report that both rabies virus strains infect activated murine lymphocytes and the human lymphoblastoid Jurkat T-cell line in vitro. The lymphocytes are more permissive to the attenuated ERA rabies virus strain than to the CVS strain in both cases. We also report that in contrast to that of the CVS strain, ERA viral replication induces apoptosis of infected Jurkat T cells, and cell death is concomitant with viral glycoprotein expression, suggesting that this protein has a role in the induction of apoptosis. Our data indicate that (i) rabies virus infects lymphocytes, (ii) lymphocyte infection with the attenuated rabies virus strain causes apoptosis, and (iii) apoptosis does not hinder rabies virus production. In contrast to CVS, ERA rabies virus and other attenuated rabies virus vaccines stimulate a strong immune response and are efficient live vaccines. The paradoxical finding that a rabies virus triggers a strong immune response despite the fact that it infects lymphocytes and induces apoptosis is discussed in terms of the function of apoptosis in the immune response.
Thoulouze
M I
MI
Département de Virologie, Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, Paris, France.
Lafage
M
M
Montano-Hirose
J A
JA
Lafon
M
M
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D002843:Chromatin / Q000648:ultrastructure; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D011820:Rabies virus / Q000472:pathogenicity / Q000502:physiology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology* / Q000821:virology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014774:Virulence; D014779:Virus Replication
D002843:Chromatin