HIV entry: a game of hide-and-fuse?

Human Immunodeficiency Virus (HIV) initiates infection by fusing its envelope membrane with the cell membrane through a process which is triggered through interactions with the cellular receptor and coreceptor. Although the mechanism of HIV fusion has been extensively studied, the point of its entry into cells remains controversial. HIV has long been thought to fuse directly with the cell plasma membrane. However, several lines of evidence suggest that endocytic entry of HIV can lead to infection and, moreover, that endocytosis could be the predominant HIV entry pathway into different cell types. This review discusses recent findings pertinent to HIV entry routes and novel approaches to pinpoint the sites of virus entry.