Membrane fusion And the Alphavirus Life Cycle

The explosion of information in modern cell biology has in many cases been fostered by the use of viruses as experimental paradigms Subjects as wide ranging as RNA splicing, DNA replication, on cogenes, cell polarity, and membrane protein biosynthesis have all taken advantage of the experimental manipulability, high signal-to-noise ratio, and defined components of virus systems. The usefulness of viruses is similarly apparent from the studies of the entry pathway of enveloped animal viruses into host cells; here, viruses have been critical to the understanding of cellular endocytic uptake and the molecular mechanisms of membrane fusion. This chapter summarizes the current understanding of the life cycle of alphaviruses, focusing in particular on their entry pathway and membrane fusion activity. Alphaviruses comprise a genus of the family Togaviridae, currently containing about 26 members, including the well-characterized prototype viruses, semliki forest virus (SFV) and sindbis virus (SV). The endocytic virus infection pathway and the involvement of low pH in triggering virus-membrane fusion were first delineated, using SFV, and this virus has remained an important tool in the study of both endocytosis and membrane fusion. Results from both SFV and SV are reviewed in this chapter, with additional information from other alphaviruses when available. The extensive literature on alphavirus replication, structure, entry, and fusion has also been summarized in a number of reviews that are cited under the appropriate section.