pH-Dependent Fusion of Vesicular Stomatitis Virus with Cells: Studies of Mechanism Based on an Allosteric Model

Abstract

Most enveloped animal viruses enter cells by receptor-mediated endocytosis through coated pits (White et al, 1983). In the endocytic vesicle rapid acidification occurs, a process which triggers fusion of the viral membrane with that of the endosome, and the nucleocapsid is ejected into the cytosol. Some viruses, such as Sendai, fuse directly with the plasma membrane at neutral pH. The viruses which enter via the endocytic pathway can be made to fuse directly with the plasma membrane by lowering the pH of the medium. In fact, a common assay for viral fusion is counting cell-cell fusion events after inducing viral-cell fusion by exposing the culture to low pH for a short time. In order to study mechanisms of viral membrane fusion it is necessary to measure the fusion of intact virions with target membranes directly. In our laboratory we are focussing on the study of mechanisms of entry of Vesicular Stomatitis Virus (VSV). The envelope of VSV consists of a bilayer membrane with a single type of spike glycoprotein, the G protein, which contains all the functions needed to induce membrane fusion (Florkiewicz and Rose, 1984). However, the structural domains responsible for those functions have not been characterized.