Mechanisms of Enveloped virus entry into cells

Enveloped animal viruses enter their host cells by a process of membrane fusion. This fusion can occur at the cell plasma membrane or within the endocytic vacuolar system, depending on the characteristics of the virus fusion protein. Examples of both pathways of viral entry are detailed in this review. Semliki Forest virus (SFV) is presented as a well-studied prototype of those viruses which use endocytic uptake in order to infect cells. Fusion of endocytosed SFV is specifically triggered by the acidic pH present within the endocytic pathway, which causes specific conformational changes in the SFV spike protein. While the overall features of endocytic uptake are similar for all viruses which use this pathway, the mechanism by which the viruses then cause fusion appears to differ significantly between them. The best understood fusion mechanism is that of influenza virus, for which sequences involved in pH-dependent fusion can be correlated with the crystallographic structure of the spike protein. In contrast to these pH-dependent virus systems, the entry of human immunodeficiency virus (HIV) into cells occurs by a pH-independent fusion mechanism probably involving fusion at the plasma membrane. The data to date on HIV fusion, endocytosis and entry are summarized as an example of this pathway.