Pathways of viral gene expression during acute neuronal infection with HSV-1.
Pathways of viral gene expression during acute neuronal infection with HSV-1.
复制标题
HSV-1 急性神经元感染期间病毒基因表达的途径。
DOI：
10.1016/0042-6822(92)90690-q
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发表时间：
1992
期刊：
影响因子：
3.7
通讯作者：
Stevens,JG
中科院分区：
文献类型：
--
作者：
Margolis,TP;Sedarati,F;Dobson,AT;Feldman,LT;Stevens,JG
在感觉神经节感染HSV-1的急性期，研究病毒基因表达的途径。为了便于这些研究，我们构建了科斯/62-3，一个HSV-1载体，其中大肠杆菌-Z基因插入病毒潜伏相关转录物启动子的两个拷贝之后。在小鼠足垫接种病毒后，通过双重免疫荧光法测定急性感染的背根神经节（DRG）神经元中β-半乳糖苷酶和HSV病毒抗原的存在。大多数感染的神经元对δ-半乳糖苷酶或病毒抗原进行染色。不到0.2%的病毒抗原染色的神经元也表达β-半乳糖苷酶，不到10%的表达δ-半乳糖苷酶的神经元也染色的病毒抗原。作为这些发现的结果，我们提出，在神经节感染的急性期，基本上有两个群体的HSV感染的神经元。在一个群体的神经元有丰富的病毒蛋白质的合成，但最小的潜伏期相关的转录，而在第二个群体的神经元病毒基因的表达受到严重限制，除了潜伏期相关的转录的合成。由于DRG神经元是一个异质性的细胞群体，我们进一步试图确定基因表达的任一途径是否更可能发生在特定的神经元表型。为了实现这一点，使用抗体来表征急性感染病毒的DRG神经元表型。结果表明，以大量潜伏期相关转录物的转录和最小病毒蛋白合成为特征的神经元感染途径更可能发生在表达细胞抗原SSEA-3的DRG神经元中。这些数据表明，神经元在调节HSV感染的结果中起着重要作用。最后，我们试图确定在建立潜伏感染的过程中是否发生DNA复制。我们发现，在神经节感染的急性期，用核苷酸类似物处理潜伏感染科斯（M）株HSV的神经元的DNA含量不受影响，这表明在潜伏感染的建立期间不发生病毒DNA复制。
Pathways of viral gene expression were investigated during the acute phase of sensory ganglionic infection with HSV-1. To facilitate these studies we constructed KOS/62-3, an HSV-1 vector in which theEscherichia colilac-Z gene was inserted behind both copies of the promoter for the viral latency-associated transcripts. Following footpad inoculation of mice with the virus, acutely infected dorsal root ganglion (DRG) neurons were assayed by dual immunofluorescence for the presence of β-galactosidase and HSV viral antigens. Most infected neurons stained for either δ-galactosidase or viral antigens. Less than 0.2% of neurons staining for viral antigens also expressed β-galactosidase, and less than 10% of neurons expressing δ-galactosidase also stained for viral antigen. As a consequence of these findings, we propose that there are essentially two populations of HSV-infected neurons during the acute phase of ganglionic infection. In one population of neurons there is abundant viral protein synthesis but minimal transcription of latency-associated transcripts, whereas in a second population of neurons viral gene expression is severely restricted except for the synthesis of latency-associated transcripts. Since DRG neurons are a heterogeneous population of cells, we further sought to determine whether either pathway of gene expression was more likely to occur in a particular neuronal phenotype. To accomplish this, antibodies were used to characterize the DRG neuronal phenotypes acutely infected with the virus. The results indicated that the pathway of neuronal infection characterized by transcription of abundant latency-associated transcripts and minimal viral protein synthesis was much more likely to occur in DRG neurons expressing the cellular antigen SSEA-3. These data indicate that the neuron plays a major role in regulating the outcome of infection with HSV. Finally, we sought to determine whether DNA replication occurs in the course of establishment of a latent infection. We found that the DNA content of neurons latently infected with KOS(M) strain HSV was not affected by treatment with nucleotide analogues during the acute phase of ganglionic infection, suggesting that viral DNA replication does not occur during the establishment of latent infection.