Tombusvirus polymerase: Structure and function

Tombusviruses are small icosahedral viruses that possess plus-sense RNA genomes ∼4.8 kb in length. The type member of the genus, tomato bushy stunt virus (TBSV), encodes a 92 kDa (p92) RNA-dependent RNA polymerase (RdRp) that is responsible for viral genome replication and subgenomic (sg) mRNA transcription. Several functionally relevant regions in p92 have been identified and characterized, including transmembrane domains, RNA-binding segments, membrane targeting signals, and oligomerization domains. Moreover, conserved tombusvirus-specific motifs in the C-proximal region of the RdRp have been shown to modulate viral genome replication, sg mRNA transcription, and trans-replication of subviral replicons. Interestingly, p92 is initially non-functional, and requires an accessory viral protein, p33, as well as viral RNA, host proteins, and intracellular membranes to become active. These and other host factors, through a well-orchestrated process guided by the viral replication proteins, mediate the assembly of membrane-associated virus replicase complexes (VRCs). Here, we describe what is currently known about the structure and function of the tombusvirus RdRp and how it utilizes host components to build VRCs that synthesize viral RNAs.