Immunosuppression in rabies virus infection mediated by lymphocyte apoptosis.
Previously, we demonstrated a depression of cell-mediated immunity in mice by street rabies virus infection. In the present study, we investigated several events during the course of infection and looked for alterations in the host lymphoid cells for evidence of apoptosis. Total cellular RNA was extracted from muscle tissues at the inoculation site of peripherally infected mice at different intervals after infection. Rabies virus mRNA was monitored by reverse transcription-PCR. The length of virus localization at the site of exposure in the muscle was as long as 5 days post-inoculation before the virus entered the central nervous system. At this inoculation site, the virus disappeared transiently between days 7 and 9 after infection but then was restored thereafter until death. Annexin V-fluorescein isothiocyanate staining of splenocytes and thymocytes from mice revealed apoptotic changes in these cells with a marked increase after day 6 of infection. Rabies virus antigen in the brain became detectable 6 days after infection; this occurred parallel to the appearance of apoptosis in the lymphoid cells. There was atrophy of the spleen and thymus, with no evidence of infection. Our results suggest that the interaction between the rabies virus and infected neurons triggers the process of lymphoid cell apoptosis, which reflects the defective operation of the immune system.
Kasempimolporn
S
S
Queen Saovabha Memorial Institute, World Health Organization Collaborating Center for Research on Rabies Pathogenesis, Bangkok 10330, Thailand. qsmiskp@redcross.or.th
Tirawatnapong
T
T
Saengseesom
W
W
Nookhai
S
S
Sitprija
V
V
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000821:virology; D004195:Disease Models, Animal; D004285:Dogs; D007165:Immunosuppression Therapy; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000235:genetics; D011818:Rabies / Q000276:immunology* / Q000821:virology; D011820:Rabies virus / Q000302:isolation & purification; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D012333:RNA, Messenger; D012367:RNA, Viral