DELINEATION OF PUTATIVE MECHANISMS INVOLVED IN ANTIBODY-MEDIATED CLEARANCE OF RABIES VIRUS FROM THE CENTRAL-NERVOUS-SYSTEM

DELINEATION OF PUTATIVE MECHANISMS INVOLVED IN ANTIBODY-MEDIATED CLEARANCE OF RABIES VIRUS FROM THE CENTRAL-NERVOUS-SYSTEM
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DOI:
10.1073/pnas.89.15.7252
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发表时间:
1992-08-01
影响因子:
11.1
通讯作者:
KOPROWSKI, H
KOPROWSKI, H
中科院分区:
综合性期刊1区
文献类型:
--
作者:
DIETZSCHOLD, B;KAO, M;KOPROWSKI, H

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比较了几种狂犬病病毒中和单抗(MAbs)的体外生物学活性和它们预防致死性狂犬病病毒脑脊髓炎的能力。特定单抗在体内的保护活性与其在体外的病毒中和活性无关;相反,它与单抗抑制病毒在细胞间传播和限制狂犬病病毒RNA转录的能力有关。由于用病毒中和单抗处理狂犬病病毒感染的细胞会导致抗体的内吞,我们假设抗体即使在被细胞摄取后也可能发挥其抑制活性。暴露后用单抗在体外抑制病毒传播和病毒RNA转录的大鼠导致病毒从中枢神经系统清除,并保护动物免受致命性狂犬病病毒的感染。
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.