GENETIC-ANALYSIS OF INVIVO-SELECTED VIRAL VARIANTS CAUSING CHRONIC INFECTION - IMPORTANCE OF MUTATION IN THE L-RNA SEGMENT OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS
GENETIC-ANALYSIS OF INVIVO-SELECTED VIRAL VARIANTS CAUSING CHRONIC INFECTION - IMPORTANCE OF MUTATION IN THE L-RNA SEGMENT OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS
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DOI：
10.1128/jvi.62.9.3301-3308.1988
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发表时间：
1988-09-01
影响因子：
5.4
通讯作者：
FREEDMAN, DM
中科院分区：
文献类型：
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作者：
AHMED, R;SIMON, RS;FREEDMAN, DM
在持续感染淋巴细胞性脉络膜脑膜炎病毒(LCMV)的小鼠的中枢神经系统(CNS)和淋巴组织中，存在着不同生物学特性的病毒变体。来自CNS的病毒分离株与最初的阿姆斯特朗LCMV株相似，在成年小鼠中诱导强大的病毒特异性T细胞反应，感染很快就被清除。相比之下，来自携带者小鼠脾的LCMV分离株会在成年小鼠中持续感染。这种慢性感染与低水平的抗病毒T细胞反应有关。在这项研究中，我们通过在脾分离株和野生型(Wt)LCMV之间制造重组体(重组体)来描述两个独立派生的脾变异体的基因特征，并表明在成年小鼠中持续存在的能力和相关的T细胞反应抑制与大的(L)rna片段分离。此外，我们还分析了一种来自其中一种脾变异体的逆转株(从中枢神经系统分离出来)。通过比较含有相同的S片段但含有原wt-Armstrong LCMV的L片段的三个重组体的生物学特性，我们能够明确地表明，L片段不仅发生在wt LCMV的脾变异株的产生过程中，而且在脾变异株向wt表型的回复过程中也发生了生物学相关的突变。因此，我们的结果表明：(1)L基因组片段的基因改变参与了病毒变异的器官特异性选择；(2)这些突变深刻地影响了巨细胞病毒在成年小鼠中引起慢性感染的能力。
Viral variants with different biological properties are present in the central nervous systems (CNS) and lymphoid tissues of mice persistently infected with lymphocytic choriomeningitis virus (LCMV). Viral isolates from the CNS are similar to the original Armstrong LCMV strain and induce potent virus-specific T-cell responses in adult mice, and the infection is rapidly cleared. In contrast, LCMV isolates derived from spleens of carrier mice cause persistent infections in adult mice. This chronic infection is associated with low levels of antiviral T-cell responses. In this study, we genetically characterized two independently derived spleen variants by making recombinants (reassortants) between the spleen isolates and wild-type (wt) LCMV and showed that the ability to persist in adult mice and the associated suppression of T-cell responses segregates with the large (L) RNA segment. In addition, we analyzed a revertant (isolated from CNS) derived from one of the spleen variants. By comparing the biological properties of three reassortants the contained the same S segment but had the L segment of either the original wt Armstrong LCMV, the spleen variant derived from it, or the CNS revertant derived from the spleen variant, we were able to show unequivocally that biologically relevant mutations occurred in the L segment not only during generation of the spleen variant from wt LCMV but also in reversion of the spleen variant to the wt phenotype. Thus, our results showed that (i) genetic alterations in the L genomic segment were involved in organ-specific selection of viral variants, and (ii) these mutations profoundly affected the ability of LCMV to cause chronic infections in adult mice.