The H gene of rodent brain-adapted measles virus confers neurovirulence to the Edmonston vaccine strain
The H gene of rodent brain-adapted measles virus confers neurovirulence to the Edmonston vaccine strain
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DOI：
10.1128/jvi.73.8.6916-6922.1999
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发表时间：
1999-08-01
影响因子：
5.4
通讯作者：
Rima, BK
中科院分区：
文献类型：
--
作者：
Duprex, WP;Duffy, I;Rima, BK
麻疹病毒（MV）的血凝素（H）蛋白中存在神经发病机制的分子决定因素。从MV的Edmonston B疫苗全长感染性克隆中产生了H基因插入载体，使用该载体，有可能将完整的H开放阅读框插入到亲本（Edtag）背景中。将来自啮齿动物脑适应MV株（CAM/RE）的H基因插入到该载体中，并用表达T7 RNA聚合酶的改良痘苗病毒（MVA-T7）拯救重组病毒（EdtagCAMH）。重组病毒的生长速度和滴度与CAM/RE加Edtag亲本病毒相当。在MV脑炎的小鼠模型中测定神经毒力。将病毒脑内注射到C57/BL/6乳小鼠的右皮质中。感染后，接种CAM/RB菌株的小鼠出现后肢麻痹和共济失调。用等量的Edtag病毒或假感染从未观察到临床症状。免疫组织化学（MC）用于检测福尔马林固定的脑切片中的病毒抗原。麻疹抗原在海马、额叶、颞叶和嗅觉皮质以及对称结构两侧的新纹状体的神经元和神经元突起中观察到。感染Edtag病毒的小鼠未检测到病毒抗原。感染重组病毒EdtagCAMH的小鼠出现临床疾病，并且通过IHC在与感染CAM/RB的动物中检测到的相似的脑区域中检测到病毒。然而，EdtagCAMH感染在感染后4天的进展远小于CAM/RB病毒。因此，似乎在MV基因组的其他区域中编码了额外的决定簇，这些决定簇是与CAM/RE等同的完全神经毒力所需的。然而，仅H基因的替换就足以引起神经病理学。
Molecular determinants of neuropathogenesis have been shown to be present in the hemagglutinin (H) protein of measles virus (MV). An H gene insertion vector has been generated from the Edmonston B vaccine full-length infectious clone of MV, Using this vector, it is possible to insert complete H open reading frames into the parental (Edtag) background. The H gene from a rodent brain-adapted MV strain (CAM/RE) was inserted into this vector, and a recombinant virus (EdtagCAMH) was rescued by using a modified vaccinia virus which expresses T7 RNA polymerase (MVA-T7), The recombinant virus grew at an equivalent rate and to similar titers as the CAM/RE add Edtag parental viruses. Neurovirulence was assayed in a mouse model for MV encephalitis. Viruses were injected intracerebrally into the right cortex of C57/BL/6 suckling mice. After infection mice inoculated with the CAM/RB strain developed hind limb paralysis and ataxia. Clinical symptoms were never observed with an equivalent dose of Edtag virus or in sham infections, Immunohistochemistry (MC) was used to detect viral antigen in formalin-fixed brain sections. Measles antigen was observed in neurons and neuronal processes of the hippocampus, frontal, temporal, and olfactory cortices and neostriatum on both sides of symmetrical structures. Viral antigen was not detected in mice infected with Edtag virus. Mice infected with the recombinant virus, EdtagCAMH, became clinically ill, and virus was detected by IHC in regions of the brain similar to those in which it was detected in animals infected with CAM/RB. The EdtagCAMH infection had, however, progressed much less than the CAM/RB virus at 4 days postinfection. It therefore appears that additional determinants are encoded in other regions of the MV genome which are required for full neurovirulence equivalent to CAM/RE. Nevertheless, replacement of the H gene alone is sufficient to cause neuropathology.