Abortive rabies virus central nervous infection is controlled by T lymphocyte local recruitment and induction of apoptosis.
Nonfatal paralysis, induced by the attenuated Pasteur strain of rabies virus, is characterised by local and irreversible flaccid paralysis of the inoculated limbs. We characterised the spread and localisation of virus in the CNS of infected mice, determined the nature of cell injury and examined the role of the immune response. Data indicate that infection of BALB/c mice induced paralysis in 60% of infected mice, the others recovering without sequelae. In both groups of mice, virus was detected in restricted sub-populations of neurons from the brain and spinal cord, and intensity of the neuropathology correlated with levels of rabies RNA and apoptotic infected neurons. However, apoptosis of neurons and paralysis were not due to a direct deleterious effect of the virus, but induced by a T-dependent immune response, as evidenced by their absence in nude mice. Paralysed and asymptomatic mice developed a similar rabies virus-specific IgG2a antibody response, thus excluding the role of any modification of the humoral immune response. In contrast, three events were critically associated with the development of neurological symptoms: the amount of virus in the CNS, the level of apoptosis in both infected neurons and uninfected surrounding cells and the progressive parenchymal infiltration of CD4+ and CD8+ T cells at the site of infection. These data suggest that during nonfatal rabies infection, the levels of viral replication and primary degeneration of infected neurons by apoptosis could be responsible for the infiltration of T lymphocytes capable of inducing secondary degeneration of neural cells.
Galelli
A
A
Department of Virology, Pasteur Institute, Paris, France.
Baloul
L
L
Lafon
M
M
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000032:analysis; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002490:Central Nervous System / Q000473:pathology / Q000821:virology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D015213:Neuroimmunomodulation / Q000276:immunology; D009474:Neurons / Q000166:cytology / Q000276:immunology / Q000821:virology; D015345:Oligonucleotide Probes; D010243:Paralysis / Q000276:immunology / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis; D011818:Rabies / Q000276:immunology* / Q000473:pathology; D011820:Rabies virus / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D014774:Virulence
D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D015345:Oligonucleotide Probes; D012333:RNA, Messenger