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 [1]. Interestingly, we have found that M also has a role in the nucleus of infected cells [2]. 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-β pathway and has a CRM-1 dependent nuclear export [3,4]. 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 [5]. 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 [6].
The data thus far show that M protein has nuclear and cytoplasmic roles that are essential for optimal virus replication, assembly and budding.