Silver-haired bat rabies virus variant does not induce apoptosis in the brain of experimentally infected mice.
To examine whether induction of apoptosis plays a role in the pathogenesis of street rabies, we compared the distribution of viral antigens, histopathology, and the induction of apoptosis in the brain of mice infected with a street rabies virus (silver-haired bat rabies virus, SHBRV) and with a mouse-adapted laboratory rabies virus strain (challenge virus standard, CVS-24). Inflammation was identified in the meninges, but not in the parenchyma of the brain of mice infected with either CVS-24 or SHBRV. Necrosis was present in numerous cortical, hippocampal, and Purkinje neurons in CVS-24-infected mice, but only minimal necrosis was identified in mice infected with SHBRV. Likewise, extensive terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) staining was observed in the brain of mice infected with CVS-24 but little or none in the brain of mice infected with SHBRV. Rabies virus antigens were distributed similarly in the CNS infected with either virus. However, the expression of the glycoprotein (G) is more widespread and the staining of G is generally stronger in CVS- than SHBRV-infected mice, whereas the expression of rabies virus nucleoprotein (N) is similar in mice infected with either CVS or SHBRV. The positive TUNEL staining thus correlates with the high level of G expression in CVS-infected mouse brain. Northern blot hybridization revealed that the ratio between the N and G transcripts is similar in brains infected with either virus, indicating that the reduced expression of G protein is not caused by reduced transcription in SHBRV-infected animals. Taken together, these observations suggest that apoptosis is not an essential pathogenic mechanism for the outcome of a street rabies virus infection and that other pathologic processes may contribute to the profound neuronal dysfunction characteristic of street rabies.
Yan
X
X
Department of Pathology, College of Veterinary Medicine, The University of Georgia, D.W. Brooks Drive, Athens, GA 30602-7388, USA.
Prosniak
M
M
Curtis
M T
MT
Weiss
M L
ML
Faber
M
M
Dietzschold
B
B
Fu
Z F
ZF
D000818:Animals; D000956:Antigens, Viral; D017209:Apoptosis; D015152:Blotting, Northern; D001921:Brain / Q000473:pathology / Q000821:virology*; D002685:Chiroptera; D006023:Glycoproteins / Q000235:genetics; D020287:In Situ Nick-End Labeling; D051379:Mice; D008813:Mice, Inbred ICR; D009336:Necrosis; D009474:Neurons / Q000473:pathology / Q000821:virology; D019251:Nucleocapsid / Q000235:genetics; D019590:Nucleocapsid Proteins; D012333:RNA, Messenger / Q000032:analysis; D011818:Rabies / Q000473:pathology*; D011820:Rabies virus / Q000472:pathogenicity*; D014759:Viral Envelope Proteins / Q000235:genetics; D014774:Virulence
D000956:Antigens, Viral; D006023:Glycoproteins; D019590:Nucleocapsid Proteins; D012333:RNA, Messenger; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus; C099601:nucleocapsid protein, Rabies virus