Degrees of maturity: the complex structure and biology of flaviviruses

Flaviviruses are small enveloped virions that enter target cells in a pH-dependent fashion. Virus attachment, entry, and membrane fusion are orchestrated by the envelope (E) and pre-membrane (prM) proteins, the two structural proteins displayed on the surface of virions. Flaviviruses assemble as an immature non-infectious form onto which prM and E form trimeric spikes. During egress from infected cells, flaviviruses undergo dramatic structural changes characterized by the formation of a herringbone arrangement of E proteins that lie flat against the surface of the virion and cleavage of the prM protein by the cellular protease furin. The result is a relatively smooth, infectious mature virion. This dynamic process is now understood in structural detail at the atomic level. However, recent studies indicate that many of the virions released from cells share structural features of both immature and mature virus particles. These mosaic partially mature virions are infectious and interact uniquely with target cells and the host immune response. Here, we will discuss recent advances in our understanding of the biology and significance of partially mature flaviviruses.