Identification of a region of hantavirus nucleocapsid protein required for RNA chaperone activity

Abstract

Sin Nombre hantavirus (SNV) is a New World hantavirus and causes hantavirus cardiopulmonary syndrome. The viral nucleocapsid protein (N) is an RNA chaperone and has multiple functions important in virus replication. The three negative sense RNA segments of hantaviruses form panhandle structures through imperfect hydrogen bonding of the 5’ and 3’ termini, and the chaperone activity of N can mediate correct panhandle formation. N also functions during transcription and translation initiation and the chaperone activity of N is likely to be involved in aspects of these processes. Using a series of mutations in the N gene we identified a region of N required for chaperone activity. The N-terminal 100 amino acids of N contain a domain that is both necessary and sufficient for RNA chaperone activity. We propose that this region of N may reside in one of two potential states. First, the region may be highly disordered and function in N-mediated RNA chaperone activity. Alternatively, in trimeric form, the region likely becomes ordered and serves in high affinity vRNA panhandle recognition.