Secondary herpes simplex virus latent infection in transplanted ganglia.
Secondary herpes simplex virus latent infection in transplanted ganglia.
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移植神经节继发性单纯疱疹病毒潜伏感染。
DOI：
10.1128/jvi.68.11.7212-7220.1994
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发表时间：
1994
影响因子：
5.4
通讯作者：
Hay,KA
中科院分区：
文献类型：
--
作者：
Tenser,RB;Edris,WA;Gaydos,A;Hay,KA
将单纯疱疹病毒（HSV）潜伏感染的感觉神经节移植到同系受者的肾包膜下，观察潜伏感染的残留情况。HSV潜伏相关转录本（LAT）的表达和HSV的再激活移植后的背根神经节外植体作为潜伏期的标志物进行监测。移植后2 - 4周，两者均表明移植物中存在HSV潜伏期的证据。在这些时间，在直接神经节匀浆中未检测到感染性病毒。病毒抗原和感染细胞多肽4 RNA均未检出。综上所述，结果表明，HSV潜伏感染，而不是持续感染存在于移植。从这些结果中，两种解释似乎是可能的：潜伏期维持在移植的神经元，或者，潜伏期开发移植后，在神经元以前没有潜伏感染。后者被认为是假定的次级潜伏期，并从三个方面进行了研究。首先，评估了可能作为继发性潜伏期来源的再激活证据。移植后3 - 5天，HSV抗原表达（52%的移植物）和无细胞病毒（38%的移植物）的存在证明了移植物中HSV的再活化。其次，在接受潜伏感染的神经节之前用HSV免疫的受者中研究了假定的次级潜伏期。免疫受体移植后3~5天未检测到再激活，3~4周后这些受体中LAT表达罕见。最后，通过比较标准HSV和再活化缺陷型胸苷激酶阴性（TK-）HSV的结果，研究了继发潜伏期的可能性。免疫组化和不能分离感染性病毒证实了TK-HSV的再活化缺陷. TK + HSV潜伏感染的供体背根神经节在移植后2周或更长时间内显示出许多LAT阳性神经元（平均每移植26个）。然而，在移植后> 2周，在用TK-HSV潜伏感染的供体神经节中，LAT表达不可检测或最小（平均，每次移植0.2）。因此，移植后TK-HSV感染的供体神经节的再活化受损与随后的有限LAT表达相关。根据这些结果，可以得出结论，对于潜伏感染TK + HSV并移植到肾包膜下的神经节，发生了继发性潜伏期。在这种移植模型中的体内再活化可能提供比通常的体外外植体模型更有用的手段来研究HSV再活化，并且可以补充其他体内再活化模型。次级潜伏期的发生是独特的。免疫系统对继发潜伏期的抑制可能提供了一种评价HSV潜伏期的免疫控制的途径。
Sensory ganglia latently infected with herpes simplex virus (HSV) were transplanted beneath the renal capsule of syngeneic recipients, and the latent infection remaining was investigated. HSV latency-associated transcript (LAT) expression and reactivation of HSV after explant of transplanted dorsal root ganglia were monitored as markers of latency. Two to four weeks after transplantation, both indicated evidence of HSV latency in transplants. At those times, infectious virus was not detected in direct ganglion homogenates. In addition, viral antigen and infected cell polypeptide 4 RNA were not detected. Taken together, the results suggested that HSV latent infection rather than persistent infection was present in transplants. From these results, two explanations seemed possible: latency was maintained in transplanted neurons, or alternatively, latency developed after transplantation, in neurons not previously latently infected. The latter was considered putative secondary latency and was investigated in three ways. First, evidence of reactivation which might serve as a source for secondary latency was evaluated. Reactivation of HSV in transplants was evident from HSV antigen expression (52% of transplants) and the presence of cell-free virus (38% of transplants) 3 to 5 days after transplantation. Second, putative secondary latency was investigated in recipients immunized with HSV prior to receiving latently infected ganglia. Reactivation was not detected 3 to 5 days after transplantation in immunized recipients, and LAT expression was rare in these recipients after 3 to 4 weeks. Lastly, the possibility of secondary latency was investigated by comparing results obtained with standard HSV and with reactivation-defective thymidine kinase-negative (TK-) HSV. Defective reactivation of TK- HSV was demonstrated by immunohistochemistry and by the inability to isolate infectious virus. Donor dorsal root ganglia latently infected with TK+ HSV showed many LAT-positive neurons 2 or more weeks after transplantation (average, 26 per transplant). However, LAT expression was undetectable or minimal > 2 weeks after transplantation in donor ganglia latently infected with TK- HSV (average, 0.2 per transplant). Impaired reactivation of TK- HSV-infected donor ganglia after transplantation, therefore, was correlated with subsequent limited LAT expression. From these results, the occurrence of secondary latency was concluded for ganglia latently infected with TK+ HSV and transplanted beneath the kidney capsule. In vivo reactivation in this transplant model may provide a more useful means to investigate HSV reactivation than in usual in vitro explant models and may complement other in vivo reactivation models. The occurrence of secondary latency was unique. The inhibition of secondary latency by the immune system may provide an avenue to evaluate immunological control of HSV latency.