Kurachi R, Daikoku T, Tsurumi T, Maeno K, Nishiyama Y, Kurata T
Laboratory of Virology, Nagoya University School of Medicine, Japan.
Arch Virol. 1993;133(3-4):259-73. doi: 10.1007/BF01313767.
We have investigated the pathogenicity of a US3 protein kinase-deficient mutant (L1 BR1) of herpes simplex virus type 2 (HSV-2) for 4-week-old ICR mice to define the role of the viral protein kinase in virus-host interaction. When mice were intraperitoneally infected with 10(5)PFU of L1 BR1, the virus disappeared from the peritoneal cavity by 2 days postinfection and failed to induce any significant histopathological changes in the liver and spleen although viral antigens were occasionally detected in the epithelial cells of small bile ducts and small vascular wall. The parental virus (HSV-2 186) and a revertant of the mutant (L1 B-11) both caused severe hepatitis, and viral antigens were clearly detected in the hepatocytes and Kupffer cells in the focal necrotic areas. Both of the virulent viruses, unlike L1 BR1, could produce infectious progeny and cytopathic effects in freshly harvested peritoneal macrophages. The growth of L1 BR1 in peritoneal macrophages was restricted at a stage of or prior to viral DNA synthesis but after the induction of viral DNA polymerase. In addition, the production and/or the spread of mutant in mouse embryo fibroblasts (MEF) was found to be much more effectively suppressed by cocultivation of peritoneal macrophages than that of 186. An almost complete inhibition of L1 BR1-plaque formation was observed at a macrophage-to-MEF ratio of 4:1. These results suggest that the attenuation of L1 BR1 following intraperitoneal infection is primarily due to its high sensitivity to intrinsic and extrinsic inhibition of peritoneal macrophages and that the US3 protein kinase may play a role in viral DNA replication in peritoneal macrophages.
我们研究了2型单纯疱疹病毒（HSV-2）的US3蛋白激酶缺陷型突变体（L1 BR1）对4周龄ICR小鼠的致病性，以确定病毒蛋白激酶在病毒-宿主相互作用中的作用。当小鼠腹腔注射10(5)PFU的L1 BR1时，感染后2天病毒从腹腔消失，尽管在小胆管上皮细胞和小血管壁中偶尔检测到病毒抗原，但未在肝脏和脾脏中诱导任何明显的组织病理学变化。亲本病毒（HSV-2 186）和突变体的回复株（L1 B-11）均引起严重肝炎，在局灶性坏死区域的肝细胞和库普弗细胞中可清楚地检测到病毒抗原。与L1 BR1不同，这两种强毒株均可在新鲜收获的腹腔巨噬细胞中产生感染性子代并产生细胞病变效应。L1 BR1在腹腔巨噬细胞中的生长在病毒DNA合成阶段或之前受到限制，但在病毒DNA聚合酶诱导之后。此外，发现腹腔巨噬细胞共培养对突变体在小鼠胚胎成纤维细胞（MEF）中的产生和/或传播的抑制作用比186更有效。在巨噬细胞与MEF的比例为4:1时，观察到L1 BR1空斑形成几乎完全受到抑制。这些结果表明，腹腔感染后L1 BR1的减毒主要是由于其对腹腔巨噬细胞内在和外在抑制的高度敏感性，并且US3蛋白激酶可能在腹腔巨噬细胞的病毒DNA复制中起作用。
