Brain Trauma Enhances Transient Cytomegalovirus Invasion of the Brain Only in Mice That Are Immunodeficient

Brain Trauma Enhances Transient Cytomegalovirus Invasion of the Brain Only in Mice That Are Immunodeficient
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DOI:
10.1128/jvi.01728-08
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发表时间:
2009-01-01
影响因子:
5.4
通讯作者:
van den Pol, Anthony N.
van den Pol, Anthony N.
中科院分区:
医学2区
文献类型:
--
作者:
van den Pol, Anthony N.

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巨细胞病毒(CMV)是导致免疫系统低下的个体神经功能障碍的最常见病毒病原体之一。CMV如何进入大脑仍然是一个悬而未决的问题。对脑损伤可能增强CMV进入脑的假设进行了检验。将无菌针头插入脑内,导致在损伤后1小时内外周接种的免疫缺陷SCID小鼠脑中的小鼠CMV急剧增加,并在1周后进行检查;损伤后48小时外周接种和1周存活仅导致损伤部位的中度感染。相比之下,未受伤的SCID小鼠以及受伤的免疫活性对照小鼠在相同的时间间隔内几乎没有病毒感染的迹象。脑直接接种导致1周后测试的SCID脑中mCMV的广泛散布和增强的复制,但在平行对照脑中没有。差异性病毒血症不太可能解释SCID脑中更高的病毒载量,因为与对照组相比,SCID血液中mCMV的增加直到更长的间隔才被检测到。这些数据表明,脑损伤增强了CMV对大脑的侵袭,但只有当适应性免疫系统受损时,大脑抵抗病毒感染的能力才能在损伤后迅速恢复。
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.