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.

The target cell tropism of enveloped viruses is regulated by interactions between viral proteins and cellular receptors determining susceptibility at a host cell, tissue or species level. However, a number of additional cell-surface moieties can also bind viral envelope glycoproteins and could act as capture receptors, serving as attachment factors to concentrate virus particles on the cell surface, or to disseminate the virus infection to target organs or susceptible cells within the host. Here, we used Junín virus (JUNV) or JUNV glycoprotein complex (GPC)-pseudotyped particles to study their ability to be internalized by the human C-type lectins hDC- or hL-SIGN. Our results provide evidence that hDC- and hL-SIGN can mediate the entry of Junín virus into cells, and may play an important role in virus infection and dissemination in the host.