Internalization and fusion mechanism of vesicular stomatitis virus and related rhabdoviruses.

Members of the Rhabdoviridae infect a wide variety of animals and plants, and are the causative agents of many important diseases. Rhabdoviruses enter host cells following internalization into endosomes, with the glycoprotein (G protein) mediating both receptor binding to host cells and fusion with the cellular membrane. The recently solved crystal structure of vesicular stomatitis virus G has allowed considerable insight into the mechanism of rhabdovirus entry, in particular the low pH-dependent conformational changes that lead to fusion activation. Rhabdovirus entry shows several distinct features compared with other enveloped viruses; first, the entry process appears to consist of two distinct fusion events, initial fusion into vesicles within endosomes followed by back-fusion into the cytosol; second, the conformational changes in the G protein that lead to fusion activation are reversible; and third, the G protein is structurally distinct from other viral fusion proteins and is not proteolytically cleaved. The internalization and fusion mechanisms of rhabdoviruses are discussed in this article, with a focus on viral systems where the G protein has been studied extensively: vesicular stomatitis virus and rabies virus, as well as viral hemorrhagic septicemia virus.