van den Pol Anthony N
Department of Neurosurgery, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520, USA.
J Virol. 2009 Jan;83(1):420-7. doi: 10.1128/JVI.01728-08. Epub 2008 Oct 22.
Cytomegalovirus (CMV) is one of the most common viral pathogens leading to neurological dysfunction in individuals with depressed immune systems. How CMV enters the brain remains an open question. The hypothesis that brain injury may enhance the entrance of CMV into the brain was tested. Insertion of a sterile needle into the brain caused a dramatic increase in mouse CMV in the brains of immunodeficient SCID mice inoculated peripherally within an hour of injury and examined 1 week later; peripheral inoculation 48 h after injury and a 1-week survival resulted in only a modest infection at the site of injury. In contrast, uninjured SCID mice, as well as injured immunocompetent control mice, showed little sign of viral infection at the same time intervals. Direct inoculation of the brain resulted in widespread dispersal and enhanced replication of mCMV in SCID brains tested 1 week later but not in parallel control brains. Differential viremia was unlikely to account for the greater viral load in the SCID brain, since increased mCMV in the blood of SCID compared to controls was not detected until a longer interval. These data suggest that brain injury enhances CMV invasion of the brain, but only when the adaptive immune system is compromised, and that the brain's ability to resist viral infection recovers rapidly after injury.
巨细胞病毒(CMV)是导致免疫系统低下个体出现神经功能障碍的最常见病毒病原体之一。CMV如何进入大脑仍是一个悬而未决的问题。脑损伤可能会增强CMV进入大脑的这一假说得到了验证。在免疫缺陷的SCID小鼠受伤后一小时内对外周进行接种,并在1周后进行检查,结果发现,向脑内插入无菌针头会导致小鼠脑中的小鼠巨细胞病毒显著增加;受伤48小时后进行外周接种并存活1周,仅在损伤部位出现适度感染。相比之下,未受伤的SCID小鼠以及受伤的具有免疫能力的对照小鼠在相同时间间隔内几乎没有病毒感染迹象。直接向脑内接种导致1周后检测的SCID小鼠脑内mCMV广泛扩散并增强复制,但在平行对照小鼠脑中则不然。不同的病毒血症不太可能解释SCID小鼠脑内更高的病毒载量,因为直到更长时间间隔后才检测到与对照相比SCID小鼠血液中mCMV增加。这些数据表明,脑损伤会增强CMV对大脑的侵袭,但仅在适应性免疫系统受损时才会如此,并且大脑抵抗病毒感染的能力在损伤后会迅速恢复。