The influence of the cytoskeleton on the development and behavior of viral factories in mammalian orthoreovirus.

Cytosolic viral factories (VFs) of mammalian orthoreovirus (MRV) are sites for viral genome replication and assembly of virus progeny. Despite advancements in reverse genetics, the formation and dynamics of VFs still need to be clarified. MRV exploits host cytoskeletal components like microtubules (MTs) throughout its life cycle, including cell entry, replication, and release. MRV VFs, membrane-less cytosolic inclusions, rely on the viral proteins μ2 and μNS for formation. Protein μ2 interacts and stabilizes MTs through acetylation, supporting VF formation and viral replication, while scaffold protein μNS influences cellular components to aid VF maturation. The disruption of the MT network reduces viral replication, underscoring its importance. Additionally, μ2 associates with MT-organizing centers, modulating the MT dynamics to favor viral replication. In summary, MRV subverts the cytoskeleton to facilitate VF dynamics and promote viral replication and assembly to promote VF dynamics, replication, and assembly, highlighting the critical role of the cytoskeleton in viral replication.