Yasuda Jiro, Hunter Eric, Nakao Mitsuyoshi, Shida Hisatoshi
Division of Molecular Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
EMBO Rep. 2002 Jul;3(7):636-40. doi: 10.1093/embo-reports/kvf132.
In this study, we have identified a novel Nedd4-like ubiquitin ligase, BUL1, as the host factor involved in budding of type D retrovirus Mason-Pfizer monkey virus (M-PMV). Overexpression of BUL1 enhanced virus particle release, while a BUL1 mutant in which a W to G substitution was introduced into a WW domain, W791G, lost the ability to bind to the viral Gag protein and abolished its ability to mediate virus budding. In addition, a fragment of BUL1 containing only the WW domains inhibited virus budding in a dominant negative manner. These results, together with previous findings, indicate that the M-PMV Gag L domain interacts with the BUL1 WW domain and that this interaction is essential for virus budding. Our observations provide new insights into the mechanism of virus budding, and could be useful in establishing new antiviral strategies targeted at progeny virus release from a host cell.
在本研究中，我们鉴定出一种新型的类Nedd4泛素连接酶BUL1，它是参与D型逆转录病毒梅森- Pfizer猴病毒（M-PMV）出芽的宿主因子。BUL1的过表达增强了病毒颗粒的释放，而在WW结构域中引入W到G替换的BUL1突变体W791G失去了与病毒Gag蛋白结合的能力，并消除了其介导病毒出芽的能力。此外，仅包含WW结构域的BUL1片段以显性负性方式抑制病毒出芽。这些结果与先前的发现一起表明，M-PMV Gag L结构域与BUL1 WW结构域相互作用，并且这种相互作用对于病毒出芽至关重要。我们的观察结果为病毒出芽机制提供了新的见解，并且可能有助于建立针对从宿主细胞释放子代病毒的新抗病毒策略。
