SIGNIFICANCE OF PREMATURE STOP CODONS IN ENV OF SIMIAN IMMUNODEFICIENCY VIRUS
SIGNIFICANCE OF PREMATURE STOP CODONS IN ENV OF SIMIAN IMMUNODEFICIENCY VIRUS
复制标题
DOI：
10.1128/jvi.63.11.4709-4714.1989
复制
发表时间：
1989-11-01
影响因子：
5.4
通讯作者：
DESROSIERS, RC
中科院分区：
文献类型：
--
作者：
KODAMA, T;WOOLEY, DP;DESROSIERS, RC
猴免疫缺陷病毒（SIVmac）的跨膜蛋白（TMP）的翻译终止密码子的位置在三个感染性分子克隆中不同。SIVmac 251和SIVmac 142感染性克隆具有提前终止信号，其位置相差一个密码子;将这些DNA转染到人HUT-78细胞中产生具有截短TMP（28至30千道尔顿[kDa]）的病毒。SIVmac 239感染性克隆在其TMP编码区没有提前终止密码子。用该克隆转染HUT-78细胞最初产生具有全长TMP（41 kDa）的病毒。在转染后20至30天，具有41-kDa TMP的SIVmac 239病毒逐渐消失，同时出现具有28-kDa TMP的病毒。病毒生产急剧增加，与出现的病毒与28 kDa的TMP平行。从这些文化的病毒DNA的序列分析表明，提前终止密码子所产生的点突变是负责的TMP的大小随时间的变化。当SIVmac 239克隆转染到人外周血淋巴细胞（PBL）中时，观察到对TMP截短形式的类似选择压力。相反，在猕猴PBL中没有观察到这种选择压力。当将SIVmac 239克隆转染到猕猴PBL中并将所得病毒在猕猴PBL中连续传代时，病毒复制得非常好，并在培养物中保持41-kDa TMP达80天。猕猴感染SIVmac 239具有28-kDa的TMP;病毒随后从T4富集的外周血淋巴细胞中回收，仅显示TMP的41-kDa形式。这些结果表明SIVmac中TMP的天然形式是全长41-kDa TMP，就像在人类免疫缺陷病毒1型中一样。具有截短形式的TMP的病毒似乎是在非天然人类细胞中繁殖期间突变和选择的结果。
The location of the translational termination codon for the transmembrane protein (TMP) varies in three infectious molecular clones of simian immunodeficiency virus from macaques (SIVmac). The SIVmac251 and SIVmac142 infectious clones have premature stop signals that differ in location by one codon; transfection of these DNAs into human HUT-78 cells yielded virus with a truncated TMP (28 to 30 kilodaltons [kDa]). The SIVmac239 infectious clone does not have a premature stop codon in its TMP-coding region. Transfection of HUT-78 cells with this clone initially yielded virus with a full-length TMP (41 kDa). At 20 to 30 days posttransfection, SIVmac239 virus with a 41-kDa TMP gradually disappeared coincident with the emergence of a virus with a 28-kDa TMP. Virus production dramatically increased in parallel with the emergence of a virus with a 28-kDa TMP. Sequence analysis of viral DNAs from these cultures showed that premature stop codons arising by point mutation were responsible for the change in size of the TMP with time. A similar selective pressure for truncated forms of TMP was observed when the SIVmac239 clone was transfected into human peripheral blood lymphocytes (PBL). In contrast, no such selective pressure was observed in macaque PBL. When the SIVmac239 clone was transfected into macaque PBL and the resultant virus was serially passaged in macaque PBL, the virus replicated very well and maintained a 41-kDa TMP for 80 days in culture. Macaque monkeys were infected with SIVmac239 having a 28-kDa TMP; virus subsequently recovered from T4-enriched lymphocytes of peripheral blood showed only the 41-kDa form of TMP. These results indicate that the natural form of TMP in SIVmac is the full-length 41-kDa TMP, just as in human immunodeficiency virus type 1. Viruses with truncated forms of TMP appear to result from mutation and selection during propagation in unnatural human cells.