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.
Highlights
Vaccinia virus (VACV) is one of the most intensively studied members of the poxvirus family, primarily as a consequence of its unprecedented success as a live viral vaccine for smallpox, which mitigated eradication of the disease
Recent electron microscopy (EM) and tomography (ET) studies have definitively shown that the dense contents in these factories contain key proteins and membrane structures that are involved in membrane biogenesis, including pre-assembled D13 scaffolds, ruptured small ER
Two types of aberrant structures were seen by EM, including short crescents located at the surface of viroplasm, which still contained proteins destined to form the cores of mature virions, and “empty” immature virion (IV)-like membranes, which appeared to be derived from smooth ER membranes
Summary
Vaccinia virus (VACV) is one of the most intensively studied members of the poxvirus family, primarily as a consequence of its unprecedented success as a live viral vaccine for smallpox, which mitigated eradication of the disease. The large size of the VACV genome makes it highly amenable to transduction with multiple coding genetic inserts of almost limitless size and scope and because it resides in the cytoplasm there is little risk of inadvertent host genome integration events occurring These fundamental and intrinsic characteristics of VACV, along with its proven capacity to generate lifelong and durable adaptive immune responses to encoded antigens, underpins its attractiveness as the basis of a robust vaccine vector platform technology. Following recent technological advances, genetic, proteomic, molecular biologic and microscopic studies have provided a more detailed picture of VACV assembly These studies have contributed to our understanding of the VACV maturation process which will facilitate the rational creation of safer and more efficient vaccine vector platforms and will potentiate the discovery of new classes of anti-viral drugs [7]. This review will endeavor 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
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