Flaviviruses

Abstract

Flavivirus genome amplification is a complex process that involves the viral RNA, cellular and viral proteins, and a sophisticated architecture of cellular membranes induced by viral infection. The viral RNA is not just a passive template; it plays an active role acquiring dynamic tertiary structures during viral replication. RNA synthesis is regulated by cis-acting elements present at the 5′- and 3′-ends of the viral genome. These elements include complementary sequences that mediate genome cyclization through direct RNA-RNA interactions. Studies from many laboratories have provided compelling evidence supporting the notion that a circular conformation of the viral RNA is essential for flavivirus RNA replication. In addition, an RNA element located within the viral 5′UTR has been found to bind the viral polymerase and promote RNA synthesis. In this chapter, we describe viral proteins and RNA structures involved in flavivirus genome amplification and provide working models that explain the need of long-range RNA-RNA interactions during viral RNA synthesis.