Abnormal processing of a recombinant feline leukemia virus envelope polyprotein and its interference with subgroup C virus infection.
Abnormal processing of a recombinant feline leukemia virus envelope polyprotein and its interference with subgroup C virus infection.
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重组猫白血病病毒包膜多蛋白的异常加工及其对C亚型病毒感染的干扰。
DOI：
10.1006/viro.1994.1349
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发表时间：
1994
期刊：
影响因子：
3.7
通讯作者：
Roy-Burman,P
中科院分区：
文献类型：
--
作者：
Bechtel,MK;Stallcup,MR;Bedgood,RM;Corey,JL;Pandey,R;Roy-Burman,P
在人转染细胞中检查了非感染性猫白血病病毒（FeLV）重组体（命名为r6 gp）的膜多聚蛋白的加工。r6 gp前病毒先前在FeLV，亚组B，GA克隆的框架内生成，其中表面糖蛋白（SU）的所有C末端氨基酸序列（除40个外）均来自内源性FeLV前病毒元件（CFE-6）。虽然r6 gp产生正常大小（85 kDa）的env糖蛋白前体，但与亲本病毒的前体不同，该产物既不另外糖基化，也不进一步加工成成熟env蛋白。生化观察结果与嵌合envpolyprotein被困在内质网（ER）的想法是一致的，并直接支持免疫荧光显微镜分析。有趣的是，嵌合蛋白在ER中的驻留特异性干扰FeLV，C亚组（Sarma）病毒感染，但不干扰亲本FeLV-B病毒感染。由于FeLV-C前病毒序列可以在感染的细胞中容易地检测到，因此似乎r6 gpenv表达没有阻断攻击病毒的进入。虽然FeLV-B和CFE-6 env基因具有广泛的整体序列同源性，但在r6 gp构建体中保留的靠近SU C末端的CFE-6可变区（VI区）与FeLV-C的同源性程度远高于FeLV-B。因此，我们提出，区域VI参与赋予ER中的envpolyprotein寡聚化的特异性，并且捕获的r6 gpenv与FeLV-C的共寡聚化是特异性干扰FeLV-C感染的原因。结果还首次证明了重组FeLVenv基因的功能异常，其结构与FeLV诱导的猫淋巴肉瘤中常见的结构相似。
Processing of theenvpolyprotein of a noninfectious feline leukemia virus (FeLV) recombinant, named r6gp, was examined in human-transfected cells. The r6gp provirus was previously generated in the frame of FeLV, subgroup B, GA clone with substitution of all but 40 C-terminal amino acid sequences of the surface glycoprotein (SU) from an endogenous FeLV provirus element (CFE-6). Although r6gp produced a normal size (85 kDa)envglycoprotein precursor, the product, unlike the precursor of the parental virus, was neither additionally glycosylated nor further processed into matureenvproteins. Biochemical observations were consistent with the idea that the chimericenvpolyprotein was trapped in the endoplasmic reticulum (ER) and were directly supported by immunofluorescence microscopy analyses. Interestingly, the residence of the chimeric protein in the ER specifically interfered with FeLV, subgroup C (Sarma) virus infection but not the parental FeLV-B virus infection. Since FeLV-C provirus sequences could be readily detected in the infected cells, it appeared that r6gpenvexpression did not block entry of the challenge virus. While FeLV-B and CFE-6envgenes share an extensive overall sequence homology, a variable region (region VI) of CFE-6 near the C-terminus of SU, which was retained in the r6gp construct, exhibits a considerably higher degree of homology to FeLV-C than FeLV-B. Thus, we propose that region VI is involved in conferring specificity for theenvpolyprotein oligomerization in the ER, and that co-oligomerization of the trapped r6gpenvwith FeLV-C is the reason for specific interference with FeLV-C infection. The results also demonstrate for the first time a functional abnormality of a recombinant FeLVenvgene which is structurally similar to those commonly detected in FeLV-induced feline lymphosarcomas.