Lactate dehydrogenase-elevating virus variants: cosegregation of neuropathogenicity and impaired capability for high viremic persistent infection
Lactate dehydrogenase-elevating virus variants: cosegregation of neuropathogenicity and impaired capability for high viremic persistent infection
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DOI：
10.3109/13550289809113501
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发表时间：
1998-10-01
影响因子：
3.2
通讯作者：
Plagemann, PGW
中科院分区：
文献类型：
--
作者：
Chen, ZY;Li, KH;Plagemann, PGW
乳酸脱氢酶病毒（LDV）的神经致病性分离株与非神经致病性分离株的不同之处在于其独特的导致麻痹性疾病的能力（年龄依赖性脊髓灰质炎，ADPM）在免疫抑制的C58和AKR小鼠中通过细胞内感染它们的前角神经元，我们最近报道了原始的神经致病性LDV分离物LDV-C-BR含有低水平的共存的非神经致病性LDV，在小鼠的混合感染中，LDV的竞争力迅速超过前者，导致再分离的LDV的神经致病性明显丧失，这与神经致病性LDV建立病毒血症持续感染的能力受损相关。在本研究中，我们确定了存在三个不同的准种在另一个原始的神经致病性LDV的ORF 5（编码的初级包膜糖蛋白VP-3 P）的cDNA克隆的序列分析分离。差异逆转录-聚合酶链反应测定的成功开发使我们能够通过重复的终点稀释来生物克隆所有三个准种。只有一个准种（LDV-v）是神经致病性的，另外两个，LDV-vP（可能与LDV-P相同）和LDV-vx（一种以前未被鉴定的新的LDV准种），是非神经致病性的，并且被发现是与几乎所有最初从携带各种其他可移植肿瘤的小鼠分离的LDV相关的常见LDV准种。神经致病性LDV-v在瘫痪小鼠的脊髓中选择性扩增，但建立持续性病毒血症感染的能力受损，并且在混合感染中迅速被LDV-VP和LDV-vx竞争，正如先前报道的LDV-C-BR。结果进一步支持我们的假设，即LDV的神经致病性和病毒血症持续性的受损能力是由相同的分子特征决定的。我们在神经致病性和非神经致病性LDV之间观察到的唯一一致的和生物学相关的分子差异是与VP-3 P的胞外域相关的聚乳糖胺聚糖链的数量。
Neuropathogenic isolates of lactate dehydrogenase virus (LDV) differ from non-neuropathogenic isolates in their unique ability to cause a paralytic disease (age-dependent poliomyelitis, ADPM) in immunosuppressed C58 and AKR mice by cytocidally infecting their anterior horn neurons, We have recently reported that an original neuropathogenic LDV isolate, LDV-C-BR, contained a low level of a coexisting non-neuropathogenic LDV which, in a mixed infection of mice, rapidly outcompeted the former resulting in apparent loss of neuropathogenicity of the reisolated LDV, This correlated with an impaired ability of the neuropathogenic LDV to establish a viremic persistent infection. In the present study we identified the presence of three different quasispecies in another original neuropathogenic LDV by sequence analysis of cDNA clones of ORF 5 (encoding the primacy envelope glycoprotein VP-3P) obtained from the isolate. Successful development of differential reverse transcription-polymerase chain reaction assays allowed us to biologically clone all three quasispecies through repeated end point dilutions. Only one of the quasispecies (LDV-v) was neuropathogenic, The other two, LDV-vP (probably the same as LDV-P) and LDV-vx (a novel LDV quasispecies that had not been previously identified), were non neuropathogenic and found to be the common LDV quasispecies associated with almost all LDVs originally isolated from mice carrying various other transplantable tumors. The neuropathogenic LDV-v became selectively amplified in the spinal cords of paralyzed mice, but possessed an impaired ability to establish a persistent viremic infection and was rapidly out-competed by LDV-VP and LDV-vx in mixed infections, just as reported previously for LDV-C-BR. The results further support our hypothesis that neuropathogenicity and impaired capability for viremic persistence of LDV are determined by the same molecular feature, The only consistent and biologically relevant molecular difference we have observed between neuropathogenic and non-neuropathogenic LDVs is the number of polylactosaminoglycan chains associated with the ectodomain of VP-3P.