4co6

Publication Abstract from PubMed

Nipah virus (NiV) is a highly pathogenic emergent paramyxovirus causing deadly encephalitis in humans. Its replication requires a constant supply of unassembled nucleoprotein (N0) in complex with its viral chaperone, the phosphoprotein (P). To elucidate the chaperone function of P, we reconstituted NiV the N0-P core complex and determined its crystal structure. The binding of the N-terminal region of P blocks the polymerization of N by interfering with subdomain exchange between N protomers and keeps N0 in an open conformation, ready to grasp an RNA molecule. We found that a peptide derived from the N-binding region of P protects cells against viral infection and demonstrated by structure-based mutagenesis that this peptide acts by inhibiting N0-P formation. These results provide new insights about the assembly of N along genomic RNA and validate the N0-P complex as a target for drug development.

Structure of Nipah virus unassembled nucleoprotein in complex with its viral chaperone.,Yabukarski F, Lawrence P, Tarbouriech N, Bourhis JM, Delaforge E, Jensen MR, Ruigrok RW, Blackledge M, Volchkov V, Jamin M Nat Struct Mol Biol. 2014 Aug 10. doi: 10.1038/nsmb.2868. PMID:25108352^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.