Huang M, Jolicoeur P
Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Québec, Canada.
J Virol. 1994 Sep;68(9):5648-55. doi: 10.1128/JVI.68.9.5648-5655.1994.
Murine AIDS (MAIDS) is characterized by severe lymphadenopathy and splenomegaly. The proliferation of the infected target B cells is also an important manifestation of the disease (M. Huang, C. Simard, D. G. Kay, and P. Jolicoeur, J. Virol. 65:6562-6571, 1991). The etiologic agent of MAIDS is a defective murine leukemia virus that is deleted of most of its pol and env genes and appears to encode a single protein, the Gag precursor Pr60gag protein. Pr60gag is myristylated and attached to the plasma membrane. To study the role myristylation on the function of Pr60gag, we have generated a myristylation-negative (Myr-) mutant of the MAIDS defective virus. We found that Myr- Pr60gag interacted less tightly with the plasma membrane. In addition, the Myr- MAIDS defective virus mutant was unable to induce expansion of infected cells and was nonpathogenic. These results emphasize the essential role of Pr60gag in the disease process. Our data also suggest that Pr60gag, once recruited to the cell membrane through its myristylation, interacts with other membrane-bound effectors to send signals to induce proliferation of the infected cells and to initiate immune dysfunctions.
鼠类艾滋病（MAIDS）的特征是严重的淋巴结病和脾肿大。受感染的靶B细胞的增殖也是该疾病的一个重要表现（M. Huang、C. Simard、D. G. Kay和P. Jolicoeur，《病毒学杂志》65:6562 - 6571，1991年）。MAIDS的病原体是一种缺陷型鼠白血病病毒，其大部分pol和env基因缺失，似乎只编码一种蛋白质，即Gag前体Pr60gag蛋白。Pr60gag被豆蔻酰化并附着于质膜。为了研究豆蔻酰化对Pr60gag功能的作用，我们构建了MAIDS缺陷病毒的豆蔻酰化阴性（Myr-）突变体。我们发现Myr- Pr60gag与质膜的结合不那么紧密。此外，Myr- MAIDS缺陷病毒突变体无法诱导受感染细胞的扩增，并且无致病性。这些结果强调了Pr60gag在疾病过程中的重要作用。我们的数据还表明，Pr60gag一旦通过其豆蔻酰化作用被募集到细胞膜上，就会与其他膜结合效应物相互作用，发出信号以诱导受感染细胞的增殖并引发免疫功能紊乱。
