PATHOGENICITY OF ANTIGENIC VARIANTS OF MURINE CORONAVIRUS JHM SELECTED WITH MONOCLONAL-ANTIBODIES

PATHOGENICITY OF ANTIGENIC VARIANTS OF MURINE CORONAVIRUS JHM SELECTED WITH MONOCLONAL-ANTIBODIES
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DOI:
10.1128/jvi.58.3.869-875.1986
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发表时间:
1986-06-01
影响因子:
5.4
通讯作者:
WEINER, LP
WEINER, LP
中科院分区:
医学2区
文献类型:
--
作者:
FLEMING, JO;TROUSDALE, MD;WEINER, LP

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为了分析嗜神经性小鼠冠状病毒JHMV的致病机理,我们用E2病毒糖蛋白的单抗筛选抗原性变异病毒。单抗J.7.2。和J.2.2被证明与E2分子的不同区域结合,用这两种抗体选择的变异体在小鼠身上表现出非常不同的疾病图景。J.7.2中选择的变异体与亲本病毒一样,具有高度毒性,并导致急性脑炎疾病。相比之下,J.2.2-选择的变异体在临床和组织学上主要导致亚急性麻痹疾病和广泛的脱髓鞘。用抗E2单抗可以很好地显示变异株和亲本病毒之间的抗原性差异。然而,在与针对另外两种JHMV结构蛋白E1或N的单抗的结合研究中,两种病毒之间没有差异。因为只有J.2.2。选择神经毒力降低的脱髓鞘变异体,这种单抗很可能识别在JHMV致病过程中特别重要的E2分子的一个亚区。
To analyze the pathogenesis of the neurotropic murine coronavirus JHMV, we used monoclonal antibodies to the E2 viral glycoprotein to select antigenic variant viruses. Monoclonal antibodies J.7.2. and J.2.2 were shown to bind to topographically distinct regions of the E2 molecule, and the variants selected with the two antibodies demonstrated very different disease pictures in mice. Variants selected with J.7.2 were, like the parental virus, highly virulent and caused an acute encephalitic illness. By contrast, J.2.2-selected variants predominantly caused a subacute paralytic disease clinically and extensive demyelination histologically. Antigenic differences among the variants and parental virus were readily demonstable with anti-E2 monoclonal antibodies. However, no differences between the viruses could be shown in binding studies with monoclonal antibodies directed against either E1 or N, the other two JHMV structural proteins. Since only J.2.2. selected demyelinating variants with reduced neurovirulence, it is likely that this monoclonal antibody recognizes a subregion of the E2 molecule that is particularly important in JHMV pathogenesis.