Chantler J K, Smyrnis L, Tai G
Department of Pathology, University of British Columbia, Vancouver, Canada.
Lab Invest. 1995 Mar;72(3):334-40.
Rubella virus (RV) can cause a wide variety of neurologic symptoms, particularly when infection occurs in utero. However, little is known about the pathogenesis of these infections and the cell types in human brain susceptible to infection have not been characterized.
Cell cultures derived from human brain tissue were examined for susceptibility to two wild-type and two vaccine strains of RV. Cell types expressing viral antigen were identified by double-label immunofluorescence with monoclonal antibodies to specific cell markers and a polyclonal anti-RV antibody. Viral yield was determined by plaque assay.
All four RV strains replicated in the brain cultures, although the titers obtained in the case of the vaccine strains were more than 100-fold lower than those found for wild-type isolates. Astrocytes appeared to be the main cell type infected, expressing large amounts of viral antigen. In contrast, oligodendrocytes were rarely productively infected, even when surrounded by infected astrocytes. Occasional neurons expressing viral antigen were also seen.
The main cell type permissive to RV infection in developing brain tissue is the astrocyte. Although not highly cytolytic, the virus may disrupt the functioning of these cells, resulting in neurologic deficits. The restricted replication of this virus in oligodendrocytes correlates with the lack of demyelination generally reported as being typical of RV neurologic disease.
风疹病毒(RV)可引发多种神经症状,尤其是在子宫内发生感染时。然而,对于这些感染的发病机制知之甚少,且人类大脑中易受感染的细胞类型尚未得到明确界定。
检测源自人类脑组织的细胞培养物对两种野生型和两种疫苗株风疹病毒的易感性。通过使用针对特定细胞标志物的单克隆抗体和多克隆抗风疹病毒抗体进行双重标记免疫荧光,鉴定表达病毒抗原的细胞类型。通过蚀斑测定法确定病毒产量。
所有四种风疹病毒株均在脑培养物中复制,尽管疫苗株获得的滴度比野生型分离株低100倍以上。星形胶质细胞似乎是主要的被感染细胞类型,表达大量病毒抗原。相比之下,少突胶质细胞很少被有效感染,即使被感染的星形胶质细胞包围。偶尔也可见表达病毒抗原的神经元。
发育中的脑组织中对风疹病毒感染允许的主要细胞类型是星形胶质细胞。尽管病毒的细胞溶解性不高,但可能会破坏这些细胞的功能,导致神经功能缺损。该病毒在少突胶质细胞中的限制性复制与通常报道的风疹病毒性疾病典型的脱髓鞘缺乏相关。