Respiratory syncytial virus (RSV) matrix protein (M) is a major virion structural protein. Similar to matrix proteins of other negative strand RNA viruses, it was predicted to have a key role in virus assembly. Interestingly, we have found that M also has a role in the nucleus of infected cells. We have shown that RSV M is localized in the nucleus of infected cells early in infection, being mostly cytoplasmic later. In the nucleus, M has functions traditionally allocated to non-structural proteins, while in the cytoplasm it is the major organizer of RSV assembly.
Using various in vitro, infected and transfected cell systems, we have shown that M is imported into the nucleus via the Importin-b pathway and has a CRM-1 dependent nuclear export. Regulated, timely nuclear import and export into the cytoplasm is required for optimal virus assembly, and mutations that impact on these processes result in lowered infectious virus titres. In the nucleus, M appears to inhibit cellular transcription and any mutation that impacts on this ability results in delayed RSV replication and reduced infectious titres. In the cytoplasm, M interacts with the RSV nucleocapsid-polymerase complex (vRNP), inhibiting its transcription activity. Recent work from our lab suggests that M probably facilitates the movement of the now inactive vRNPs to the site of RSV assembly at the plasma membrane. M also associates with the envelope glycoproteins at lipid rafts, the site of RSV assembly. M probably brings the vRNP and glycoproteins together via dimerization to initiate the budding process. Any changes to M’s dimerization ability impact RSV budding.
The data thus far show that M protein has nuclear and cytoplasmic roles that are essential for optimal virus replication, assembly and budding.