Basic information and current topics regarding Flaviviridae

Virus Assembly

The exact process by which a flavivirus assembles is still unknown, but it is known that viral proteins are created in the rough ER then transported through several regions to reach the plasma membrane2, where the finished virus then exits via exocytosis. Two models exist that attempt to explain how and where a flavivirus assembles into the completed particle: one in which the virus is assembled via accumulation of large vesicles containing individual particles at the trans-GA, and one where the virus is assembled at the plasma membrane.

The presence of these multiple models has lead to the suggestion that flavivirus assembly differs depending on what type of cell it is infecting. Though, the limited genome would present evidence against this idea–since having more than one working method of infection within the same viral genome is rare.

Despite which model is correct for flaviviruses, the end product is most certainly known. Capsid protein forms and the flavivirus’s genome is incorporated while the E protein is exported to be integrated into the host membrane. Once the nucleocapsid has arrived at the cell membrane, it is ready to exit the cell after a final modification of the prM protein.

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Figure 1. Predicted layout of polyprotein prior to cleavage by the various listed proteases. Black arrows show viral protease cleavage at the indicated sites and the blue/red arrows show host protease cleavage sites.
Image from Umareddy, I (2007). (see references for full citation)1

The prM proteins, as discussed previously, are important to the correct folding of the E proteins, and snipping them before releasing the virus from the plasma membrane is a must in order to have functional virus. The protein sequence at which the prM is cleaved corresponds to the protease furin, which is abundant within the trans-golgi network. Cleavage of prM at this sequence on the prM (arg-X-arg/lys-arg) represents the final step in creating adequately infectious virions.


1. Umareddy, I (2007). Dengue virus serotype infection specifies the activation of the unfolded protein response. Virology journal (1743-422X), 4, p. 91.

2. Mackenzie, JM (11/2001). Assembly and maturation of the flavivirus Kunjin virus appear to occur in the rough endoplasmic reticulum and along the secretory pathway, respectively. Journal of virology (0022-538X), 75 (22), p. 10787.