Coupling of replication and assembly in flaviviruses

•Flavivirus replication occurs on modified ER membranes called vesicle packets (Vp) and membrane vesicles (Ve).•Flavivirus non-structural proteins are implicated in membrane rearrangements.•Viral replication and assembly appear to be tightly coupled.•Non-structural proteins are important for virus assembly and budding.•Cellular lipids play an essential role in membrane rearrangements, virus assembly and budding.

Flaviviruses affect hundreds of millions of people each year causing tremendous morbidity and mortality worldwide. This genus includes significant human pathogens such as dengue, West Nile, yellow fever, tick-borne encephalitis and Japanese encephalitis virus among many others. The disease caused by these viruses can range from febrile illness to hemorrhagic fever and encephalitis. A deeper understanding of the virus life cycle is required to foster development of antivirals and vaccines, which are an urgent need for many flaviviruses, especially dengue. The focus of this review is to summarize our current knowledge of flaviviral replication and assembly, the proteins and lipids involved therein, and how these processes are coordinated for efficient virus production.