Lokensgard J R, Cheeran M C, Gekker G, Hu S, Chao C C, Peterson P K
Institute for Brain and Immune Disorders, Minneapolis Medical Research Foundation, Minnesota 55404, USA.
J Hum Virol. 1999 Mar-Apr;2(2):91-101.
To characterize replication patterns and cytopathic effects during human cytomegalovirus (HCMV) infection of brain cells.
Primary human mixed glial/neuronal cells, as well as purified microglial, astroglial, and enriched neuronal cell cultures, were infected with HCMV strains AD169 and RC256 to determine the ability of the different brain cell types to support viral replication.
Mixed glial/neuronal cell cultures were fully permissive for viral replication. Based on previous studies, we hypothesized that human microglial cells would preferentially support productive HCMV replication. However, HCMV did not replicate or display genomic expression in microglial cells. In contrast, primary astrocytes were fully permissive and displayed HCMV-induced cytopathic effects resulting in cell death. In highly enriched neuronal cultures, productive infection and viral expression occurred only in scattered astrocytes. Early in the infection, apoptotic plasma membrane changes were induced in astrocytes. However, nuclear fragmentation was not apparent until later during the course of infection.
These results suggest that HCMV possesses astrocytotropic properties that confer preferential expression and cytopathic replication in astrocytes over microglia or neuronal cells. Apoptotic cell death, which is a result of HCMV infection, appears to be delayed until peak viral replication has occurred.
描述人巨细胞病毒（HCMV）感染脑细胞期间的复制模式和细胞病变效应。
用人混合神经胶质/神经元细胞以及纯化的小胶质细胞、星形胶质细胞和富集的神经元细胞培养物感染HCMV毒株AD169和RC256，以确定不同类型脑细胞支持病毒复制的能力。
混合神经胶质/神经元细胞培养物对病毒复制完全易感。基于先前的研究，我们假设人小胶质细胞会优先支持HCMV的有效复制。然而，HCMV在小胶质细胞中不复制或不显示基因组表达。相反，原代星形胶质细胞对HCMV完全易感，并表现出HCMV诱导的细胞病变效应，导致细胞死亡。在高度富集的神经元培养物中，有效感染和病毒表达仅发生在散在的星形胶质细胞中。在感染早期，星形胶质细胞诱导了凋亡性质膜变化。然而，直到感染后期核碎裂才明显。
这些结果表明，HCMV具有嗜星形胶质细胞特性，使其在星形胶质细胞中比小胶质细胞或神经元细胞更易优先表达和进行细胞病变性复制。作为HCMV感染结果的凋亡性细胞死亡似乎会延迟到病毒复制达到峰值时才出现。
