Role of a membrane glycoprotein in Friend virus erythroleukemia: nucleotide sequences of nonleukemogenic mutant and spontaneous revertant viruses.
Role of a membrane glycoprotein in Friend virus erythroleukemia: nucleotide sequences of nonleukemogenic mutant and spontaneous revertant viruses.
复制标题
膜糖蛋白在弗兰德病毒红白血病中的作用：非白血病突变体和自发回复病毒的核苷酸序列。
DOI：
10.1128/jvi.57.2.534-538.1986
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发表时间：
1986
影响因子：
5.4
通讯作者：
Kabat,D
中科院分区：
文献类型：
--
作者：
Li,JP;Bestwick,RK;Machida,C;Kabat,D
我们以前分离的朋友脾病灶形成病毒的自发env基因突变体，在成年小鼠中是nonleukemogenic的，但在新生儿中形成致白血病的回复突变体，我们发现，回复突变体含有二级env突变。为了确定其致病功能的重要的编码膜糖蛋白的网站，我们分子克隆和部分测序的两个突变病毒（克隆63和克隆4）和一个回复突变体（克隆4 REV）的env基因。克隆63含有三个非连续的点突变，导致env糖蛋白的异嗜性相关结构域中Gly-119----Arg-119、Cys-180----Tyr-180和Gly-203----Arg-203的非保守氨基酸取代。这些取代大概是负责改变电泳和致病特性的突变糖蛋白。这些和其他几个G-A核苷酸取代在不同的网站在一个自发突变体的存在提供了惊人的证据，错误丰富的前病毒可以在逆转录病毒复制过程中形成。克隆4含有在氨基酸残基304（Gln-304-Ochre-304）处产生提前终止密码子的点突变。该终止密码子位于建议的异嗜性-嗜亲性重组位点之后，并消除了嗜亲性相关结构域，包括糖蛋白的假定膜锚。克隆4 REV是来源于克隆4的真回复突变体，其中提前终止密码子已回复突变以重新形成野生型序列。这些结果证实了朋友脾病灶形成病毒的发病机制中的env基因的重要作用，并建议编码的膜糖蛋白包含不同的结构域，有助于其致病功能。
We previously isolated spontaneous env gene mutants of Friend spleen focus-forming virus that are nonleukemogenic in adult mice but form leukemogenic revertants in newborns; we found that the revertants contain secondary env mutations. To identify sites in the encoded membrane glycoprotein that are important for its pathogenic function, we molecularly cloned and partially sequenced the env genes of two mutant viruses (clone 63 and clone 4) and one revertant (clone 4REV). Clone 63 contained three noncontiguous point mutations that caused nonconservative amino acid substitutions of Gly-119----Arg-119, Cys-180----Tyr-180, and Gly-203----Arg-203 in the xenotropic-related domain of the env glycoprotein. These substitutions were presumably responsible for the altered electrophoretic and pathogenic properties of the mutant glycoprotein. The presence of these and several other G-A nucleotide substitutions at different sites in one spontaneous mutant provided striking evidence that error-rich proviruses can form during retroviral replication. Clone 4 contained a point mutation that generated a premature termination condon at amino acid residue 304 (Gln-304----Ochre-304). This termination codon was located immediately after the proposed xenotropic-ecotropic recombination site and eliminated the ecotropic-related domain, including the putative membrane anchor of the glycoprotein. Clone 4REV was a true revertant derived from clone 4 in which the premature termination codon had back-mutated to re-form the wild-type sequence. These results confirm an essential role for the env gene in Friend spleen focus-forming virus pathogenesis and suggest that the encoded membrane glycoprotein contains different domains that contribute to its pathogenic function.