Negative and ambisense RNA viruses are the causative agents of important human diseases such as
influenza,
measles,
Lassa fever, and
Ebola hemorrhagic fever. The viral genome of these RNA viruses consists of one or more single-stranded
RNA molecules that are encapsidated by viral
nucleocapsid proteins to form a
ribonucleoprotein complex (RNP). This RNP acts as protection, as a scaffold for RNA folding, and as the context for viral replication and transcription by a
viral RNA polymerase. However, the roles of the
viral nucleoproteins extend beyond these functions during the
viral infection cycle. Recent advances in structural biology techniques and analysis methods have provided new insights into the formation, function, dynamics, and evolution of negative sense virus
nucleocapsid proteins, as well as the role that they play in host innate immune responses against
viral infection. In this review, we discuss the various roles of
nucleocapsid proteins, both in the context of RNPs and in
RNA-free states, as well as the open questions that remain.