Hajek K L, Friesen P D
Graduate Program in Cellular and Molecular Biology, Graduate School and College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
J Virol. 1998 Nov;72(11):8718-24. doi: 10.1128/JVI.72.11.8718-8724.1998.
TED (transposable element D) is an env-containing member of the gypsy family of retrotransposons that represents a possible retrovirus of invertebrates. This lepidopteran (moth) retroelement contains gag and pol genes that encode proteins capable of forming viruslike particles (VLP) with reverse transcriptase. Since VLP are likely intermediates in TED transposition, we investigated the roles of gag and pol in TED capsid assembly and maturation. By using constructed baculovirus vectors and TED Gag-specific antiserum, we show that the principal translation product of gag (Pr55(gag)) is cleaved to produce a single VLP structural protein, p37(gag). Replacement of Asp436 within the retrovirus-like active site of the pol-encoded protease (PR) abolished Pr55(gag) cleavage and demonstrated the requirement for PR in capsid processing. As shown by expression of an in-frame fusion of TED gag and pol, PR is derived from the Gag-Pol polyprotein Pr195(gag-pol). The PR cleavage site within Pr55(gag) was mapped to a position near the junction of a basic, nucleocapsid-like domain and a C-terminal acidic domain. Once released by cleavage, the C-terminal fragment was not detected. This acidic fragment was dispensable for VLP assembly, as demonstrated by the formation of VLP by C-terminal Pr55(gag) truncation proteins and replacement of the acidic domain with a heterologous protein. In contrast, C-terminal deletions that extended into the adjacent nucleocapsid-like domain of Pr55(gag) abolished VLP recovery and demonstrated that this central region contributes to VLP assembly or stability, or both. Collectively, these data suggest that the single TED protein p37(gag) provides both capsid and nucleocapsid functions. TED may therefore use a simple processing strategy for VLP assembly and genome packaging.
TED(转座元件D)是逆转录转座子吉普赛家族中一个包含env的成员,它代表了一种可能的无脊椎动物逆转录病毒。这种鳞翅目(蛾类)逆转录元件包含gag和pol基因,这些基因编码的蛋白质能够与逆转录酶一起形成病毒样颗粒(VLP)。由于VLP可能是TED转座过程中的中间体,我们研究了gag和pol在TED衣壳组装和成熟中的作用。通过使用构建的杆状病毒载体和TED Gag特异性抗血清,我们发现gag的主要翻译产物(Pr55(gag))被切割产生一种单一的VLP结构蛋白p37(gag)。在pol编码的蛋白酶(PR)的逆转录病毒样活性位点内替换Asp436消除了Pr55(gag)的切割,并证明了衣壳加工过程中对PR的需求。如TED gag和pol的读码框内融合表达所示,PR来自Gag-Pol多蛋白Pr195(gag-pol)。Pr55(gag)内的PR切割位点被定位到一个靠近碱性核衣壳样结构域和C末端酸性结构域交界处的位置。一旦通过切割释放,C末端片段未被检测到。如C末端Pr55(gag)截短蛋白形成VLP以及用异源蛋白替换酸性结构域所证明的,这个酸性片段对于VLP组装是可有可无的。相比之下,延伸到Pr55(gag)相邻核衣壳样结构域的C末端缺失消除了VLP的回收,并证明这个中心区域对VLP组装或稳定性或者两者都有贡献。总的来说,这些数据表明单一的TED蛋白p37(gag)兼具衣壳和核衣壳功能。因此,TED可能使用一种简单的加工策略来进行VLP组装和基因组包装。