Defect in entry and altered pathogenicity of a polyoma virus mutant blocked in VP2 myristylation.
Defect in entry and altered pathogenicity of a polyoma virus mutant blocked in VP2 myristylation.
复制标题
VP2肉豆蔻酰化受阻的多瘤病毒突变体的进入缺陷和致病性改变。
DOI：
10.1006/viro.1993.1016
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发表时间：
1993
期刊：
影响因子：
3.7
通讯作者：
Benjamin,T
中科院分区：
文献类型：
--
作者：
Sahli,R;Freund,R;Dubensky,T;Garcea,R;Bronson,R;Benjamin,T
我们研究了多瘤病毒次要衣壳蛋白VP2和VP3突变的影响。突变体感染细胞后，通过改变启动子蛋氨酸密码子阻断VP2或VP3的表达，导致野生型逆转录物的快速选择。这种逆转表明，病毒生长对这两种蛋白质的需求即使不是绝对的，也是很强的。一种突变病毒VP2*，其中丙氨酸取代了甘氨酸-2，表达了一种非肉芽化形式的VP2，该VP2被整合到病毒粒子中。研究表明，与野生型病毒相比，VP2*在原代和已建立的小鼠细胞中的特异性感染性降低了15至20倍，并延迟了生长。对生长延迟的分析表明，在感染的早期阶段，在脱衣时或之前，存在缺陷。与野生型感染细胞相比，突变体中病毒DNA和VP1的合成延迟了约9小时。没有证据表明它对病毒组装（包衣）或病毒粒子的稳定性有影响。VP2*突变病毒感染小鼠后，病毒复制和肿瘤诱导减弱，鼻内接种比腹腔接种受到更严重的影响。
We have examined effects of mutations of the minor capsid proteins VP2 and VP3 of polyoma virus. Infection of cells by mutants blocked in expression of either VP2 or VP3 by alterations of their initiator methionine codons led to the rapid selection of wild-type revertants. This reversion suggests a strong, if not absolute, requirement for both proteins in virus growth. A mutant virus, VP2*, in which alanine was substituted for glycine-2, expressed a nonmyristylated form of VP2 that was incorporated into virions. Studies of VP2*revealed a 15- to 20-fold lower specific infectivity and a delay in growth in both primary and established mouse cells compared to wild-type virus. Analysis of the growth delay indicated a defect in an early step of infection, at or prior to uncoating. Synthesis of viral DNA and VP1 was delayed by about 9 hr in mutant compared to that in wild-type infected cells. No evidence was obtained for an effect on either virus assembly (encapsidation) or stability of virions. Infection of mice by the VP2*mutant virus resulted in attenuated virus replication and tumor induction which were much more severely affected following intranasal inoculation than intraperitoneal inoculation.