Lipopolysaccharide, tumor necrosis factor alpha, or interleukin-1β triggers reactivation of latent cytomegalovirus in immunocompetent mice
Lipopolysaccharide, tumor necrosis factor alpha, or interleukin-1β triggers reactivation of latent cytomegalovirus in immunocompetent mice
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DOI：
10.1128/jvi.00216-06
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发表时间：
2006-09-01
影响因子：
5.4
通讯作者：
Sedmak, Daniel D.
中科院分区：
文献类型：
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作者：
Cook, Charles H.;Trgovcich, Joanne;Sedmak, Daniel D.
我们先前已经证明，巨细胞病毒（CMV）可以重新激活的非免疫抑制患者的肺部在危重病。我们最近的工作表明，多微生物细菌败血症可以触发潜伏的小鼠CMV（MCMV）的再激活。我们推测细菌性脓毒症后MCMV的再激活可能是由炎症介质引起的。为了验证这一假设，BALB/c小鼠潜伏感染史密斯株MCMV接受亚致死剂量的脂多糖（LPS），肿瘤坏死因子α（TNF-α），白细胞介素-1 β（IL-1 β），或盐水腹腔内。在介质注射后3周评价肺组织匀浆的病毒再活化。因为已知LPS在小鼠中通过Toll样受体4（TLR-4）发出信号，所以使用单克隆XITS 510进行阻断该信号传导机制的进一步研究。最后，用静脉注射TNF-α测试小鼠，以确定这是否会导致再激活。所有接受亚致死腹腔内剂量LPS、TNF-α或IL-1 β的小鼠在注射后3周均出现潜伏MCMV的肺再活化，LPS引起MCMV再活化的动力学与脓毒症相似。当TLR-4信号被阻断时，外源性LPS不能重新激活潜伏的MCMV。静脉注射近致死剂量的TNF-α不会使MCMV重新激活。外源性腹膜内LPS、TNF-α和IL-1 β都能够重新激活先前健康小鼠肺中潜伏的CMV。MCMV的LPS再活化似乎依赖于TLR-4信号传导。有趣的是，静脉注射TNF-α并没有触发再激活，这表明可能的机制差异进行了讨论。我们的结论是，炎症性疾病状态，除了败血症可能能够重新激活CMV从潜伏期。
We have previously shown that cytomegalovirus (CMV) can reactivate in lungs of nonimmunosuppressed patients during critical illness. Our recent work has shown that polymicrobial bacterial sepsis can trigger reactivation of latent murine CMV (MCMV). We hypothesize that MCMV reactivation following bacterial sepsis may be caused by inflammatory mediators. To test this hypothesis, BALB/c mice latently infected with Smith strain MCMV received sublethal intraperitoneal doses of lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), or saline. Lung tissue homogenates were evaluated for viral reactivation 3 weeks after mediator injection. Because LPS is known to signal via Toll-like receptor 4 (TLR-4) in mice, further studies blocking this signaling mechanism were performed using monoclonal XITS510. Finally, mice were tested with intravenous TNF-alpha to determine whether this would cause reactivation. All mice receiving sublethal intraperitoneal doses of LPS, TNF-alpha, or IL-1 beta had pulmonary reactivation of latent MCMV 3 weeks following injection, and LPS caused MCMV reactivation with kinetics similar to those for sepsis. When TLR-4 signaling was blocked, exogenous LPS did not reactivate latent MCMV. Intravenous TNF-alpha administration at near-lethal doses did not reactivate MCMV. Exogenous intraperitoneal LPS, TNF-alpha, and IL-I beta are all capable of reactivating CMV from latency in lungs of previously healthy mice. LPS reactivation of MCMV appears dependent on TLR-4 signaling. Interestingly, intravenous TNF-alpha did not trigger reactivation, suggesting possible mechanistic differences that are discussed. We conclude that inflammatory disease states besides sepsis may be capable of reactivating CMV from latency.