Markovitz N S, Baunoch D, Roizman B
The Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Illinois 60637, USA.
J Virol. 1997 Jul;71(7):5560-9. doi: 10.1128/JVI.71.7.5560-5569.1997.
Wild-type herpes simplex virus 1 (HSV-1) multiplies, spreads, and rapidly destroys cells of the murine central nervous system (CNS). In contrast, mutants lacking both copies of the gamma(1)34.5- gene have been shown to be virtually lacking in virulence even after direct inoculation of high-titered virus into the CNS of susceptible mice (J. Chou, E. R. Kern, R. J. Whitley, and B. Roizman, Science 250:1262-1266, 1990). To investigate the host range and distribution of infected cells in the CNS of mice, 4- to 5-week-old mice were inoculated stereotaxically into the caudate/putamen with 3 x 10(5) PFU of the gamma(1)34.5- virus R3616. Four-micrometer-thick sections of mouse brains removed on day 3, 5, or 7 after infection were reacted with a polyclonal antibody directed primarily to structural proteins of the virus and with antibodies specific for neurons, astrocytes, or oligodendrocytes. This report shows the following: (i) most of the tissue damage caused by R3616 was at the site of injection, (ii) the virus spread by retrograde transport from the site of infection to neuronal cell nuclei at distant sites and to ependymal cells by cerebrospinal fluid, (iii) the virus infected neurons, astrocytes, oligodendrocytes, and ependymal cells and hence did not discriminate among CNS cells, (iv) viral replication in some neurons could be deduced from the observation of infected astrocytes and oligodendrocytes at distant sites, and (v) infected cells were being efficiently cleared from the nervous system by day 7 after infection. We conclude that the gamma(1)34.5- attenuation phenotype is reflected in a gross reduction in the ability of the virus to replicate and spread from cell to cell and is not due to a restricted host range. The block in viral replication appears to be a late event in viral replication.
野生型单纯疱疹病毒1型（HSV-1）在小鼠中枢神经系统（CNS）中繁殖、扩散并迅速破坏细胞。相比之下，已证明缺乏γ(1)34.5基因两个拷贝的突变体即使在将高滴度病毒直接接种到易感小鼠的中枢神经系统后，其毒力也几乎丧失（J. Chou、E. R. Kern、R. J. Whitley和B. Roizman，《科学》250:1262 - 1266，1990年）。为了研究小鼠中枢神经系统中感染细胞的宿主范围和分布，将4至5周龄的小鼠通过立体定位法接种3×10⁵ 个噬斑形成单位（PFU）的γ(1)34.5⁻病毒R3616到尾状核/壳核中。在感染后第3、5或7天取出的小鼠脑4微米厚切片，用主要针对病毒结构蛋白的多克隆抗体以及针对神经元、星形胶质细胞或少突胶质细胞的特异性抗体进行反应。本报告显示如下：（i）R3616引起的大部分组织损伤位于注射部位；（ii）病毒通过逆行运输从感染部位扩散到远处的神经元细胞核，并通过脑脊液扩散到室管膜细胞；（iii）病毒感染神经元、星形胶质细胞、少突胶质细胞和室管膜细胞，因此对中枢神经系统细胞没有选择性；（iv）从远处部位感染的星形胶质细胞和少突胶质细胞的观察结果可以推断出一些神经元中的病毒复制情况；（v）感染后第7天，感染细胞正从神经系统中被有效清除。我们得出结论，γ(1)34.5⁻减毒表型反映在病毒在细胞间复制和传播能力的大幅降低，而不是由于宿主范围受限。病毒复制的阻断似乎是病毒复制后期的事件。
