Koyanagi Naoto, Imai Takahiko, Arii Jun, Kato Akihisa, Kawaguchi Yasushi
Division of Molecular Virology, Department of Microbiology and Immunology; Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-Ku, Tokyo, 108-8639, Japan.
Microbiol Immunol. 2014 Jan;58(1):31-7. doi: 10.1111/1348-0421.12108.
Us3 is a serine-threonine protein kinase that is encoded by herpes simplex virus 1 (HSV-1). In experimental animal models of HSV infection, peripheral and intracranial inoculations can be used to study viral pathogenicity in peripheral sites (e.g., eyes and vagina) and central nervous systems (CNSs), respectively. In addition, peripheral inoculation can be used to investigate this virus' ability to invade the CNS (neuroinvasiveness) from peripheral sites. HSV-1 Us3 has previously been shown to be critical for viral pathogenicity in both peripheral sites and CNSs of mice. However, the role of HSV-1 Us3 in viral neuroinvasiveness has not yet been elucidated. In the present study, the yields of a Us3 null mutant virus and its repaired virus in the eyes, trigeminal ganglia, and brains of mice following ocular inoculation were examined. It was found that, although the repaired virus appeared in the brains of mice 3 days after infection, peak replication occurring 7 days after infection, no viral replication of the Us3 null mutant virus was detectable. These findings indicate that HSV-1 Us3 plays a crucial role in the ability of the virus to invade the brain from the eyes. Thus, HSV-1 Us3 is a significant neuroinvasiveness factor in vivo.
Us3是一种丝氨酸 - 苏氨酸蛋白激酶，由单纯疱疹病毒1型（HSV - 1）编码。在HSV感染的实验动物模型中，外周接种和颅内接种可分别用于研究病毒在外周部位（如眼睛和阴道）和中枢神经系统（CNS）中的致病性。此外，外周接种可用于研究该病毒从外周部位侵入CNS的能力（神经侵袭性）。先前已证明HSV - 1 Us3对小鼠外周部位和CNS中的病毒致病性至关重要。然而，HSV - 1 Us3在病毒神经侵袭性中的作用尚未阐明。在本研究中，检测了眼部接种后Us3缺失突变病毒及其修复病毒在小鼠眼睛、三叉神经节和脑中的产量。结果发现，虽然修复病毒在感染后3天出现在小鼠脑中，感染后7天出现复制高峰，但未检测到Us3缺失突变病毒的病毒复制。这些发现表明，HSV - 1 Us3在病毒从眼睛侵入大脑的能力中起关键作用。因此，HSV - 1 Us3是体内一种重要的神经侵袭因子。
