Yu Shuyuarn F, Eastman Scott W, Linial Maxine L
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Traffic. 2006 Aug;7(8):966-77. doi: 10.1111/j.1600-0854.2006.00448.x. Epub 2006 Jun 2.
Foamy viruses (FV) are unusual retroviruses that differ in many aspects of their life cycle from the orthoretroviruses such as human immunodeficiency virus. Similar to Mason-Pfizer monkey virus (MPMV), FV assemble into capsids intracellularly. The capsids are then transported to a cellular membrane for acquisition of envelope (Env) glycoproteins and budding. However, unlike MPMV, budding of FV is dependent upon the presence of Env. Previous work suggested that FV Env proteins are localized to the endoplasmic reticulum (ER) where budding takes place. However, very little was known about the details of FV assembly. We have used immunofluorescence and electron microscopy to visualize the intracellular location of FV assembly and budding. We have found that, as in the case of MPMV, FV capsids assemble at a pericentriolar site in the cytoplasm. Surprisingly, FV Env is mostly absent from this site and, contrary to expectations, FV capsid structural protein (Gag) is absent from the ER. Gag and Env only co-localize at the trans-Golgi network, suggesting that Env-Gag interactions that are required for viral egress from the cell, occurs at this site. Finally, inhibitor studies suggest an important role of microtubule networks for foamy viral assembly and budding.
泡沫病毒(FV)是一类不同寻常的逆转录病毒,其生命周期在许多方面与诸如人类免疫缺陷病毒等正逆转录病毒不同。与梅森- Pfizer猴病毒(MPMV)类似,FV在细胞内组装成衣壳。然后衣壳被转运到细胞膜以获取包膜(Env)糖蛋白并出芽。然而,与MPMV不同的是,FV的出芽依赖于Env的存在。先前的研究表明,FV Env蛋白定位于发生出芽的内质网(ER)。然而,关于FV组装的细节知之甚少。我们利用免疫荧光和电子显微镜来观察FV组装和出芽的细胞内位置。我们发现,与MPMV的情况一样,FV衣壳在细胞质中的中心粒周位点组装。令人惊讶的是,该位点大多没有FV Env,并且与预期相反,ER中没有FV衣壳结构蛋白(Gag)。Gag和Env仅在反式高尔基体网络中共定位,这表明病毒从细胞中释放所需的Env - Gag相互作用发生在该位点。最后,抑制剂研究表明微管网络在泡沫病毒组装和出芽中起重要作用。