Steiner I, Spivack J G, Deshmane S L, Ace C I, Preston C M, Fraser N W
Wistar Institute, Philadelphia, Pennsylvania 19104-4268.
J Virol. 1990 Apr;64(4):1630-8. doi: 10.1128/JVI.64.4.1630-1638.1990.
Vmw65, a herpes simplex virus type 1 (HSV-1) tegument protein, in association with cellular proteins, transactivates viral immediate early genes. In order to examine the role of Vmw65 during acute and latent infection in vivo, a mutant virus (in1814), containing a 12-base-pair insertion in the Vmw65 gene, which lacks the transactivating function of Vmw65 (C. I. Ace, T. A. McKee, J. M. Ryan, J. M. Cameron, and C. M. Preston, J. Virol. 63:2260-2269, 1989) was examined in mice. Following corneal inoculation, the parental virus (17+) and the revertant (1814R) replicated effectively in eyes and trigeminal ganglia with 30 to 60% mortality. At either equal PFU or equal particle numbers, in1814 did not replicate in trigeminal ganglia and none of the infected mice died. Although in1814 did not replicate following corneal inoculation, it established latent infection in trigeminal ganglia. HSV-1 in1814 reactivated at explant as efficiently and rapidly as did 17+ and 1814R. Even low amounts of inoculated in1814 (10(2) PFU) were sufficient to establish latent infection in some animals. Since infectious in1814 was not detected at any time in mouse trigeminal ganglia, in1814 provided a unique opportunity to determine how soon after primary infection latency begins. Latent in1814 infection was detected shortly after virus reached the sensory ganglia, between 24 to 48 h postinfection. Thus, though Vmw65 may be required for lytic infection in vivo, it is dispensable for the establishment of and reactivation from latent infection. These data support the hypotheses that the latent and lytic pathways of HSV-1 are distinct and that latency is established soon after infection without a requirement for viral replication. However, the levels of Vmw65 reaching neuronal nuclei may be a critical determinant of whether HSV-1 forms a lytic or latent infection.
Vmw65是单纯疱疹病毒1型（HSV-1）的一种包膜蛋白，它与细胞蛋白结合，可反式激活病毒的立即早期基因。为了研究Vmw65在体内急性感染和潜伏感染过程中的作用，我们在小鼠中检测了一种突变病毒（in1814），该病毒在Vmw65基因中有一个12个碱基对的插入，缺乏Vmw65的反式激活功能（C. I. Ace、T. A. McKee、J. M. Ryan、J. M. Cameron和C. M. Preston，《病毒学杂志》63:2260 - 2269，1989）。角膜接种后，亲代病毒（17 +）和回复株（1814R）在眼和三叉神经节中有效复制，死亡率为30%至60%。在相同的空斑形成单位（PFU）或相同的粒子数下，in1814在三叉神经节中不复制，且没有感染的小鼠死亡。尽管in1814角膜接种后不复制，但它能在三叉神经节中建立潜伏感染。HSV-1 in1814在外植体中重新激活的效率和速度与17 +和1814R相同。即使接种少量的in1814（10² PFU）也足以在一些动物中建立潜伏感染。由于在小鼠三叉神经节中任何时候都未检测到有感染性的in1814，in1814提供了一个独特的机会来确定初次感染后潜伏感染开始的时间。在病毒到达感觉神经节之后不久，即感染后24至48小时，就检测到了in1814的潜伏感染。因此，尽管Vmw65可能是体内溶细胞性感染所必需的，但它对于潜伏感染的建立和重新激活是可有可无的。这些数据支持以下假说：HSV-1的潜伏途径和溶细胞途径是不同的，并且潜伏感染在感染后不久就建立，无需病毒复制。然而，到达神经元细胞核的Vmw65水平可能是HSV-1形成溶细胞性感染还是潜伏感染的关键决定因素。
