Kumaraswamy Guttalu K, Fu Ming Ming, Docherty John J
Department of Microbiology, Immunology and Biochemistry, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272, USA.
J Neurovirol. 2006 Oct;12(5):365-74. doi: 10.1080/13550280600970417.
To study early events of neonatal herpes simplex virus (HSV) encephalitis and its sequelae, the authors induced a controlled infection in the brains of mice using HSVgH, a genetically modified Disabled Infective Single Cycle virus. Neonatal Balb/C mice were infected with various amounts of HSVgH- virus by intracerebral injection. Results showed that the survival of infected mice was dependent on the amount of virus injected. Infection with 200,000 plaque forming units (pfu) of HSVgH-, virus resulted in 0% survival, whereas 25,000 pfu resulted in 75% survival. If the mice died, 98% of the deaths occurred between 3 and 7 days after infection. Replication competent virus was recovered from 20% of mice brains infected with 25,000 pfu of HSVgH-. Neutralizing antibodies were not detected 6 weeks post infection in sera of mice, which survived infection with 25,000 pfu of HSVgH-. LacZ histochemistry and immunoperoxidase staining using anti-HSV and anti- beta-galactosidase antibodies revealed that the infection was limited to the site of injection. Tissue destruction was observed at the site of inoculation 3 days post infection using cresyl violet staining. At 3 days post infection adjacent sections showed positive cells for viral antigens and apoptotic cells in the infected area. Immunoperoxidase staining using antibodies to surface markers showed microglial activation beginning on day 1 and astrocyte proliferation beginning on day 3 post infection. B and T lymphocytes were not detected on day 1 through 7 post infection. This controlled experimental HSV infection suggests a limited non-specific early host response in the neonate to HSV encephalitis.
为研究新生儿单纯疱疹病毒（HSV）脑炎及其后遗症的早期事件，作者使用HSVgH（一种基因改造的失活感染单循环病毒）在小鼠脑内诱导可控感染。通过脑内注射，将不同剂量的HSVgH-病毒感染新生的Balb/C小鼠。结果显示，感染小鼠的存活率取决于注射的病毒量。注射200,000个空斑形成单位（pfu）的HSVgH-病毒导致存活率为0%，而25,000 pfu则导致存活率为75%。若小鼠死亡，98%的死亡发生在感染后3至7天。从感染25,000 pfu HSVgH-的20%小鼠脑内可回收具有复制能力的病毒。感染25,000 pfu HSVgH-后存活的小鼠血清在感染6周后未检测到中和抗体。使用抗HSV和抗β-半乳糖苷酶抗体的LacZ组织化学和免疫过氧化物酶染色显示，感染局限于注射部位。感染后3天，使用甲酚紫染色在接种部位观察到组织破坏。感染后3天，相邻切片显示感染区域有病毒抗原阳性细胞和凋亡细胞。使用表面标志物抗体的免疫过氧化物酶染色显示，感染后第1天开始有小胶质细胞活化，第3天开始有星形胶质细胞增殖。感染后第1天至第7天未检测到B和T淋巴细胞。这种可控的实验性HSV感染提示新生儿对HSV脑炎的早期非特异性宿主反应有限。
