Biology and Molecular Genetics

Poxviruses produce two morphologically distinct infectious particles, mature virions (MVs) and extracellular virions (EVs). During replication, some MVs differentiate and become wrapped with cellular membranes, transported to the periphery, and exported as EVs. Some orthopoxviruses, e.g., cowpox virus (CPXV), form large, discrete cytoplasmic inclusions called A-type inclusion bodies (ATIs) within which MVs are embedded by a process called occlusion. ATIs are composed of aggregates of the A-type inclusion protein (ATIp), which is truncated in orthopoxviruses such as vaccinia virus (VACV) that fail to form ATIs. VACV does encode a functional A26p, which along with the ATIp is required for occlusion. A26 lacks a transmembrane domain, and nothing is known regarding how it associates with the MV and regulates occlusion. Additionally, little is known about the formation of ATIs and how MVs become embedded within them. Here, experiments show that A26p is incorporated into MVs by the A27p-A17p complex and interacts with A25p, a truncated form of the CPXV ATIp. Restoration of the full-length ATI gene is sufficient for VACV ATI formation and the occlusion of MVs. A26p directl