Visualization of Retroviral Replication in Living Cells Reveals Budding into Multivesicular Bodies

作者：Nathan M. Sherer, Maik Joerg Lehmann, Luisa F. Jiménez Soto, Alyssa Ingmundson, Stacy M. Horner, Gregor Cicchetti, Philip G. Allen, Marc Pypaert, James M. Cunningham, Walther Mothes · 发表于：Traffic · 年份：2003 · DOI：10.1034/j.1600-0854.2003.00135.x · 被引用次数：416 · 研究领域：HIV Research and Treatment、Mosquito-borne diseases and control、Cytomegalovirus and herpesvirus research

Retroviral assembly and budding is driven by the Gag polyprotein and requires the host-derived vacuolar protein sorting (vps) machinery. With the exception of human immunodeficiency virus (HIV)-infected macrophages, current models predict that the vps machinery is recruited by Gag to viral budding sites at the cell surface. However, here we demonstrate that HIV Gag and murine leukemia virus (MLV) Gag also drive assembly intracellularly in cell types including 293 and HeLa cells, previously believed to exclusively support budding from the plasma membrane. Using live confocal microscopy in conjunction with electron microscopy of cells generating fluorescently labeled virions or virus-like particles, we observed that these retroviruses utilize late endosomal membranes/multivesicular bodies as assembly sites, implying an endosome-based pathway for viral egress. These data suggest that retroviruses can interact with the vps sorting machinery in a more traditional sense, directly linked to the mechanism by which cellular proteins are sorted into multivesicular endosomes.