From crescent to mature virion: vaccinia virus assembly and maturation

Abstract

Vaccinia virus (VACV) has achieved unprecedented success as a live viral vaccine for smallpox which mitigated eradication of the disease. Vaccinia virus has a complex virion morphology and recent advances have been made to answer some of the key outstanding questions, in particular, the origin and biogenesis of the virion membrane, the transformation from immature virion (IV) to mature virus (MV), and the role of several novel genes, which were previously uncharacterized, but have now been shown to be essential for VACV virion formation. This new knowledge will undoubtedly contribute to the rational design of safe, immunogenic vaccine candidates, or effective antivirals in the future. This review endeavors to provide an update on our current knowledge of the VACV maturation processes with a specific focus on the initiation of VACV replication through to the formation of mature virions.

Figure 1

Model of Vaccinia virus (VACV) crescent membrane formation. Early transcribed protein L2 associates with the ER membrane and recruits it to viral factories, then L2 interacts with A30.5 or other unidentified proteins to rupture the ER membrane into small sections, while A14 and A17 are synthesized in the membrane in a co-translational fashion. Smooth membrane structures are recruited, opened up, and presented to pre-assembled scaffolds of D13, where D13 interacts with A17 to form crescent precursors. A11 stabilizes the end of the crescent to prevent it resealing, whereas A6 may play a role in transporting or controlling the transient association of A11 with the crescent end.

Figure 2

A summary of the transition of immature virion (IV) to mature virion (MV). I7 proteolysis has a role in removing the D13 scaffold by proteolytic processing of the membrane protein A17 (1). Core proteins are also cleaved by I7 into their mature forms (2). In the absence of the D13 scaffold the IV transitions towards becoming a MV and possibly involves rearrangement of the IV membrane into an inner and outer membrane (3). G1 activity is required to complete core condensation (4). The resulting MV contains a biconcave core that contains the viral genome and core proteins including the transcription apparatus required for early gene transcription. Lateral bodies are located outside of the core and enclosed by the MV membrane. The MV membrane contains additional proteins which can have functions that facilitate progression to enveloped MV (EV).