Delineation of putative mechanisms involved in antibody-mediated clearance of rabies virus from the central nervous system.
The in vitro biological activities of several rabies virus-neutralizing monoclonal antibodies (mAbs) were compared with their ability to prevent a lethal rabies virus encephalomyelitis. The protective activity of a particular mAb in vivo did not correlate with its virus-neutralizing activity in vitro; rather it was related to the mAb's ability to inhibit virus spread from cell to cell and to restrict rabies virus RNA transcription. Since treatment of rabies virus-infected cells with virus-neutralizing mAbs results in an endocytosis of the antibody, we hypothesize that an antibody may exert its inhibitory activity even after uptake by the cell. Post-exposure treatment of rats with a mAb that inhibited both virus spread and virus RNA transcription in vitro resulted in viral clearance from the central nervous system and protected the animals against a lethal rabies virus infection.
Dietzschold
B
B
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19109.
Kao
M
M
Zheng
Y M
YM
Chen
Z Y
ZY
Maul
G
G
Fu
Z F
ZF
Rupprecht
C E
CE
Koprowski
H
H
D000199:Actins / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D001921:Brain / Q000382:microbiology*; D002213:Capsid / Q000235:genetics; D002460:Cell Line; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009500:Neutralization Tests; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D011818:Rabies / Q000276:immunology*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D051381:Rats; D011917:Rats, Inbred Lew; D014158:Transcription, Genetic; D014758:Viral Core Proteins / Q000235:genetics
D000199:Actins; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D012367:RNA, Viral; D014758:Viral Core Proteins