Viral infection is frequently assayed by ongoing expression of viral genes. These assays fail to identify cells that have been exposed to the virus but limit or inhibit viral replication. To address this limitation, we used a dual-labeling vesicular stomatitis virus (DL-VSV), which has a deletion of the viral glycoprotein gene, to allow evaluation of primary infection outcomes. This virus encodes Cre, which can stably mark any cell with even a minimal level of viral gene expression. Additionally, the virus encodes GFP, which distinguishes cells with higher levels of viral gene expression, typically due to genome replication. Stereotactic injections of DL-VSV into the murine brain showed that different cell types had very different responses to the virus. Almost all neurons hosted high levels of viral gene expression, while glial cells varied in their responses. Astrocytes (Sox9+) were predominantly productively infected, while oligodendrocytes (Sox10+) were largely abortively infected. Microglial cells (Iba1+) were primarily uninfected. Furthermore, we monitored the early innate immune response to viral infection and identified unique patterns of interferon (IFN) induction. Shortly after infection, microglia were the main producers of IFNb , whereas later, oligodendrocytes were the main producers. IFNb + cells were primarily abortively infected regardless of cell type. Last, we investigated whether IFN signaling had any impact on the outcome of primary infection and did not observe significant changes, suggesting that intrinsic factors are likely responsible for determining the outcome of primary infection.

中文翻译：

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VSV 体内递送后中枢神经系统细胞类型的流产和生产性感染


病毒感染经常通过病毒基因的持续表达来检测。这些测定无法识别已暴露于病毒的细胞，但限制或抑制病毒复制。为了解决这一限制，我们使用了双标记水泡性口炎病毒（DL-VSV），该病毒删除了病毒糖蛋白基因，以评估原发感染结果。这种病毒编码 Cre，它可以稳定地标记任何细胞，即使病毒基因表达水平最低。此外，该病毒编码 GFP，可区分具有较高病毒基因表达水平的细胞，这通常是由于基因组复制所致。将 DL-VSV 立体定向注射到小鼠大脑中表明，不同的细胞类型对病毒的反应截然不同。几乎所有神经元都具有高水平的病毒基因表达，而神经胶质细胞的反应各不相同。星形胶质细胞 (Sox9+) 主要被高效感染，而少突胶质细胞 (Sox10+) 主要被流产感染。小胶质细胞 (Iba1+) 基本上未感染。此外，我们监测了对病毒感染的早期先天免疫反应，并确定了干扰素 (IFN) 诱导的独特模式。感染后不久，小胶质细胞是IFNb的主要产生者，而后来，少突胶质细胞是主要产生者。无论细胞类型如何，IFNb + 细胞主要被流产感染。最后，我们研究了 IFN 信号传导是否对原发感染的结果有任何影响，并且没有观察到显着的变化，这表明内在因素可能决定原发感染的结果。