Recombinant Lassa virus RING finger protein Z (Z)

Function

Plays a crucial role in virion assembly and budding. Expressed late in the virus life cycle, it acts as an inhibitor of viral transcription and RNA synthesis by interacting with the viral polymerase L. Presumably recruits the NP encapsidated genome to cellular membranes at budding sites via direct interaction with NP. Plays critical roles in the final steps of viral release by interacting with host TSG101, a member of the vacuolar protein-sorting pathway and using other cellular host proteins involved in vesicle formation pathway. The budding of the virus progeny occurs after association of protein Z with the viral glycoprotein complex SSP-GP1-GP2 at the cell periphery, step that requires myristoylation of protein Z. Also selectively represses protein production by associating with host eIF4E(PubMed:12970458, PubMed:14990716). In cell-based minigenome assay, has an inhibitory effect on the ribonucleoprotein machinery (vRNP), which is responsible for the replication and transcription of the viral genome (By similarity). Myristoylation and oligomerization of protein Z are not required for its inhibitory vRNP activity, but myristoylation probably plays a role in assembly and budding (By similarity)

Subcellular Location

Virion; Host cytoplasm, host perinuclear region; Host cell membrane (Lipid-anchor)

Subunit

Monomer (PubMed:26912609). Homododecamer; ring-like structure (PubMed:26912609). Interacts with protein NP; this interaction probably directs the encapsidated genome to budding sites (By similarity). Interacts (via RING domain) with polymerase L; this interaction inhibits viral transcription and replication, Z partially blocks the product exit tunnel for the releasing nascent RNA product. Interacts with the glycoprotein complex; this interaction plays a role in virion budding. Interacts with host eIF4E; this interaction results in eIF4E reduced affinity for its substrate, the 5'-m7 G cap structure. Interacts (via late-budding domain) with host TSG101; this interaction is essential for budding and release of viral particles. Interacts with host RPLP0; this interaction may serve to load ribosome-like particles inside the virion. Interacts with host PML; this interaction induces PML bodies redistribution in the cytoplasm upon viral infection. Interacts with host TAX1BP1 (PubMed:30909570)

• Djavani M. et al. Completion of the Lassa fever virus sequence and identification of a RING finger open reading frame at the L RNA 5' End. — Virology (1997)
• Hajjaj A. et al. PubMed: CI-8I8NGENGI5F16 (MAY-)
• Borden K.L. et al. An arenavirus RING (zinc-binding) protein binds the oncoprotein promyelocyte leukemia protein (PML) and relocates PML nuclear bodies to the cytoplasm. — J. Virol. (1998)
• Strecker T. et al. Lassa virus Z protein is a matrix protein and sufficient for the release of virus-like particles. — J. Virol. (2003)
• Cornu T.I. et al. Cells expressing the RING finger Z protein are resistant to arenavirus infection. — J. Virol. (2004)
• Eichler R. et al. Characterization of the Lassa virus matrix protein Z: electron microscopic study of virus-like particles and interaction with the nucleoprotein (NP). — Virus Res. (2004)
• Perez M. et al. Myristoylation of the RING finger Z protein is essential for arenavirus budding. — J. Virol. (2004)
• Urata S. et al. Cellular factors required for Lassa virus budding. — J. Virol. (2006)