Phenotype of a herpes simplex virus type 1 mutant that fails to express immediate-early regulatory protein ICP0
Phenotype of a herpes simplex virus type 1 mutant that fails to express immediate-early regulatory protein ICP0
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DOI：
10.1128/jvi.78.4.1763-1774.2004
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发表时间：
2004-02-01
影响因子：
5.4
通讯作者：
Orr, A
中科院分区：
文献类型：
--
作者：
Everett, RD;Boutell, C;Orr, A
单纯疱疹病毒1型（HSV-1）即早期（IE）调节蛋白ICPO是感染细胞有效进展为生产性裂解感染所必需的，特别是在有限传代的人成纤维细胞的低多重性感染中。我们已经使用了基于单细胞的检测，允许在限制性细胞类型的低多重性感染中详细分析ICPO无效表型。主要结论如下：（i）存在一个阈值输入多重数，高于该阈值输入多重数，突变病毒正常复制;（ii）低于该阈值输入多重数感染的单个细胞很可能建立非生产性感染;（iii）这些非生产性感染的细胞在感染后6 h很可能表达IE产物;（iv）即使在感染后24 × 111，IE蛋白阳性的非生产性感染的人成纤维细胞的数量也超过导致噬斑形成的细胞的数量多达2个数量级;（v）在一定比例的非生产性感染的细胞中，单个IE蛋白的表达是不完全协调的;（vi）所述非生产性细胞也可以低频率和随机方式表达早期基因产物;和（vii）通过细胞死亡，大量以低多样性被ICPO缺陷型病毒感染的人成纤维细胞丢失。我们提出，在ICPO表达的情况下，HSV-1感染的人成纤维细胞可以经历各种各样的命运，包括静止，在各种不同阶段停滞感染，细胞死亡，以及对于少数群体，开始形成斑块。
Herpes simplex virus type 1 (HSV-1) immediate-early (IE) regulatory protein ICPO is required for efficient progression of infected cells into productive lytic infection, especially in low-multiplicity infections of limited-passage human fibroblasts. We have used single-cell-based assays that allow detailed analysis of the ICPO-null phenotype in low-multiplicity infections of restrictive cell types. The major conclusions are as follows: (i) there is a threshold input multiplicity above which the mutant virus replicates normally; (ii) individual cells infected below the threshold multiplicity have a high probability of establishing a nonproductive infection; (iii) such nonproductively infected cells have a high probability of expressing IE products at 6 h postinfection; (iv) even at 24 111 postinfection, IE protein-positive nonproductively infected human fibroblast cells exceed the number of cells that lead to plaque formation by up to 2 orders of magnitude; (v) expression of individual IE proteins in a proportion of the nonproductively infected cells is incompletely coordinated; (vi) the nonproductive cells can also express early gene products at low frequencies and in a stochastic manner; and (vii) significant numbers of human fibroblast cells infected at low multiplicity by an ICPO-deficient virus are lost through cell death. We propose that in the absence of ICPO expression, HSV-1 infected human fibroblasts can undergo a great variety of fates, including quiescence, stalled infection at a variety of different stages, cell death, and, for a minor population, initiation of formation of a plaque.