Genetic basis of viral persistence: single amino acid change in the viral glycoprotein affects ability of lymphocytic choriomeningitis virus to persist in adult mice.
Genetic basis of viral persistence: single amino acid change in the viral glycoprotein affects ability of lymphocytic choriomeningitis virus to persist in adult mice.
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病毒持久性的遗传基础：病毒糖蛋白的单氨基酸变化会影响淋巴细胞性绒毛膜炎病毒在成年小鼠中持续存在的能力。
DOI：
10.1084/jem.172.4.1043
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发表时间：
1990-10-01
影响因子：
15.3
通讯作者：
Ahmed, R
中科院分区：
文献类型：
--
作者：
Matloubian, M;Somasundaram, T;Kolhekar, S R;Selvakumar, R;Ahmed, R
这项研究已经确定了病毒糖蛋白中的一个氨基酸变化，它深刻地影响了淋巴细胞性脉络丛脑膜炎病毒（LCMV）在其自然宿主中的持续生存能力。成年免疫能力小鼠感染Armstrong毒株的一种变体，脾脏分离克隆13 (svA/svA)，携带病毒数月，并表现出抑制的T细胞反应。相比之下，成年小鼠感染含有脾脏变异的L段和亲本wt Armstrong的S段的重组病毒（svA/wtA），可产生有效的lcmv特异性CTL反应，并在2-4周内清除感染。这两种病毒，即脾脏变异克隆13和重组svA/wtA，在它们的非编码区是相同的，除了糖蛋白上的一个替换外，它们的任何病毒基因都没有氨基酸变化。重组病毒svA/wtA在糖蛋白氨基酸残基260处有一个苯丙氨酸，而脾变异克隆13在该位置有一个亮氨酸。这项研究是首次在整个动物水平上定义病毒持续存在的遗传基础的报告之一，并确定了一个显著提高病毒在其自然宿主中持续存在能力的单一突变。
This study has identified a single amino acid change in the viral glycoprotein that profoundly affects the ability of lymphocytic choriomeningitis virus (LCMV) to persist in its natural host. Adult immunocompetent mice infected with a variant of the Armstrong strain, spleen isolate clone 13 (svA/svA), harbor virus for several months and exhibit suppressed T cell responses. In contrast, adult mice infected with a reassortant virus (svA/wtA) that contains the L segment of the spleen variant and the S segment of the parental wt Armstrong, make potent LCMV-specific CTL responses and clear the infection within 2-4 wk. These two viruses, spleen variant clone 13 and the reassortant svA/wtA, are identical in their noncoding regions and show no amino acid changes in any of their viral genes except for one substitution in the glycoprotein. The reassortant virus svA/wtA has a phenylalanine at amino acid residue 260 of the glycoprotein, whereas the spleen variant clone 13 has a leucine at this position. This study constitutes one of the first reports defining the genetic basis of viral persistence at the whole animal level, and identifying a single mutation that markedly increases the ability of a virus to persist in its natural host.