An endoplasmic reticulum retrieval signal partitions human foamy virus maturation to intracytoplasmic membranes
An endoplasmic reticulum retrieval signal partitions human foamy virus maturation to intracytoplasmic membranes
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DOI：
10.1128/jvi.73.9.7210-7217.1999
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发表时间：
1999-09-01
影响因子：
5.4
通讯作者：
Mulligan, MJ
中科院分区：
文献类型：
--
作者：
Goepfert, PA;Shaw, K;Mulligan, MJ
在所有逆转录病毒中，泡沫病毒（FV）是独特的，因为它们定期在胞质膜内成熟。FV的包膜糖蛋白编码内质网（ER）检索信号，即双赖氨酸基序（KKXX），其功能是将人FV（HFV）糖蛋白定位于ER。本研究分析了双赖氨酸基序在HFV感染性分子克隆中的功能，该克隆编码双赖氨酸基序中的突变。电子显微镜（EM）显示，野生型和突变型病毒的细胞质内和质膜上都有病毒体出芽。此外，突变病毒保留了它们的感染性，但缺乏二赖氨酸信号的病毒比野生型病毒在质膜上出芽的程度更大。有趣的是，这种跨质膜出芽的相对增加并没有增加病毒颗粒向细胞培养基中的总体释放，如通过病毒颗粒中的蛋白质水平或感染性病毒滴度所测量的。我们的结论是HFV的二赖氨酸基序对病毒成熟的位点施加了部分限制，但对病毒的感染性不是必需的。
Among all retroviruses, foamy viruses (FVs) are unique in that they regularly mature at intracytoplasmic membranes. The envelope glycoprotein of FV encodes an endoplasmic reticulum (ER) retrieval signal, the dilysine motif (KKXX), that functions to localize the human FV (HFV) glycoprotein to the ER. This study analyzed the function of the dilysine motif in the context of infectious molecular clones of HFV that encoded mutations in the dilysine motif. Electron microscopy (EM) demonstrated virion budding both intracytoplasmically and at the plasma membrane for the wild-type and mutant viruses. Additionally, mutant viruses retained their infectivity, but viruses lacking the dilysine signal budded at the plasma membrane to a greater extent than did wild-type viruses. Interestingly, this relative increase in budding across the plasma membrane did not increase the overall release of viral particles into cell culture media as measured by protein levels in viral pellets or infectious virus titers. We conclude that the dilysine motif of HFV imposes a partial restriction on the site of viral maturation but is not necessary for viral infectivity.