Lomniczi B, Gielkens A, Csobai I, Ben-Porat T
J Virol. 1987 Jun;61(6):1772-80. doi: 10.1128/JVI.61.6.1772-1780.1987.
The genome of pseudorabies virus consists of two components, short (S) and long (L). Only the S component is bracketed by inverted repeats, and only the S component inverts itself relative to the L component, giving rise to two isomeric forms of the genome. An attenuated vaccine strain of pseudorabies virus (Norden), however, has a genome which is found in four isomeric forms (B. Lomniczi, M. L. Blankenship, and T. Ben-Porat, J. Virol. 49:970-979, 1984). To determine the basis for the atypical structure of the genome of the Norden strain, we examined more than 40 field isolates of pseudorabies virus; all contained genomes in which the L component was fixed in only one orientation relative to the S component. Several independently generated vaccine strains which have been passaged extensively in chicken embryos and chicken embryo fibroblast (CEF) cell cultures were also analyzed; they possessed an invertible L component. Furthermore, emergence of pseudorabies virus variants with an invertible L component was observed after passage of the virus in CEF, but not in rabbit kidney or pig kidney, cells. The invertibility of the L component was associated consistently with a translocation of sequences from the left end of the genome to a position next to the inverted repeat sequence of the S component. Three observations indicate that genomes with an invertible L component (and the translocation) have a selective growth advantage over standard pseudorabies virus when grown in CEF. The proportion of virions with such genomes does not increase linearly as would be expected if the translocation events occurred repeatedly, most genomes eventually experiencing the translocation. Instead, after a lag, the proportion of such virions in the population increases relatively rapidly. The genome structures that are generated upon independent passage in CEF of each virion population were relatively homogeneous. Some heterogeneity was observed at relatively early stages of the emergence of the genomes carrying the translocation; at later stages, virions with genomes with a specific size translocation predominated in the virus population. Parallel passages in CEF of the same pseudorabies virus strain resulted in the emergence of populations of virions with genomes with different size translocations. However, in each of the passaged populations of virions the majority of virions had genomes with the same size translocation. The most likely interpretation of these results is that virions with genomes carrying the translocations that emerge upon passage of the virus in CEF have a selective advantage when grown in these cells.
伪狂犬病病毒的基因组由两个部分组成，短片段（S）和长片段（L）。只有S片段两侧有反向重复序列，并且只有S片段相对于L片段自身发生倒转，从而产生基因组的两种异构体形式。然而，一种伪狂犬病病毒减毒疫苗株（诺登株）的基因组却以四种异构体形式存在（B. 洛姆尼茨、M. L. 布兰肯希普和T. 本 - 波拉特，《病毒学杂志》49:970 - 979, 1984年）。为了确定诺登株基因组非典型结构的基础，我们检测了40多个伪狂犬病病毒的野外分离株；所有分离株的基因组中，L片段相对于S片段仅以一种方向固定。我们还分析了几种在鸡胚和鸡胚成纤维细胞（CEF）培养物中经过大量传代的独立产生的疫苗株；它们具有可倒转的L片段。此外，观察到伪狂犬病病毒在CEF中传代后出现了具有可倒转L片段的变异株，但在兔肾或猪肾细胞中传代时未出现。L片段的可倒转性始终与基因组序列从左端易位到S片段反向重复序列旁边的位置相关。有三个观察结果表明，具有可倒转L片段（以及易位）的基因组在CEF中生长时比标准伪狂犬病病毒具有选择性生长优势。具有此类基因组的病毒粒子比例并非如易位事件反复发生时预期的那样呈线性增加，大多数基因组最终都会经历易位。相反，经过一段延迟期后，群体中此类病毒粒子的比例相对迅速增加。每个病毒粒子群体在CEF中独立传代时产生的基因组结构相对均一。在携带易位的基因组出现的相对早期阶段观察到了一些异质性；在后期阶段，具有特定大小易位基因组的病毒粒子在病毒群体中占主导。同一伪狂犬病病毒株在CEF中的平行传代导致出现了具有不同大小易位基因组的病毒粒子群体。然而，在每个传代的病毒粒子群体中，大多数病毒粒子具有相同大小易位的基因组。对这些结果最可能的解释是，病毒在CEF中传代时出现的具有携带易位基因组的病毒粒子在这些细胞中生长时具有选择性优势。
