Insights into Paramyxovirus Nucleocapsids from Diverse Assemblies

Abstract

All paramyxoviruses, which include the mumps virus, measles virus, Nipah virus, Newcastle disease virus, and Sendai virus, have non-segmented single-stranded negative-sense RNA genomes. These RNA genomes are enwrapped throughout the viral life cycle by nucleoproteins, forming helical nucleocapsids. In addition to these helical structures, recombinant paramyxovirus nucleocapsids may occur in other assembly forms such as rings, clam-shaped structures, and double-headed nucleocapsids; the latter two are composed of two single-stranded helices packed in a back-to-back pattern. In all of these assemblies, the neighboring nucleoprotein protomers adopt the same domain-swapping mode via the N-terminal arm, C-terminal arm, and recently disclosed N-hole. An intrinsically disordered region in the C-terminal domain of the nucleoproteins, called the N-tail, plays an unexpected role in regulating the transition among the different assembly forms that occurs with other viral proteins, especially phosphoprotein. These structures, together with the helical nucleocapsids, significantly enrich the structural diversity of the paramyxovirus nucleocapsids and help explain the functions of these diverse assemblies, including RNA genome protection, transcription, and replication, as well as encapsulation.

The Role of Nucleoprotein in Immunity to Human Negative-Stranded RNA Viruses—Not Just Another Brick in the Viral Nucleocapsid

“…NP plays a key role in such an organized packing of the viral genome. Since the details of the NP structure and RNC assembly are beyond the scope of this review and comprehensive reviews have recently been published [ 37 , 38 , 39 , 40 ], only the basics will be presented and discussed, with a focus on those aspects especially related to further reading of this text.…”

“…To prevent this from happening, NP is chaperoned by P (or VP35 of the Ebola virus [ 50 ]), which maintains NP as a monomer and sequesters it from binding to any host RNA, thus preventing the formation of premature and empty virion. The assembly of the nucleocapsid occurs via the domain-swapping mechanism, where the NTD is essential while the CTD seems to be dispensable [ 40 ]. The very terminal region of the CTD, called the N-tail, is an intrinsically highly disordered region [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ].…”

“…In addition to NP, P participates in orchestrated activities during these structural transitions. Unexpectedly, the N-tail is essential for regulating the structural transition from one assembly form to another by interacting with the disordered N-terminal region and the C-terminal X domain of P. The docking of the complex of P-RdRp during viral replication/transcription is also governed by its interaction with the N-tail [ 74 ], probably initiating the uncoiling of nucleocapsids [ 40 ].…”

CryoEM of Viral Ribonucleoproteins and Nucleocapsids of Single-Stranded RNA Viruses

“…Other RNP-like particle structures have been solved in recent years by cryoEM for other paramyxoviruses (e.g., a cetacean morbillivirus or Sendai virus) [ 44 , 45 ]. Additional reviews specific to the nucleocapsid structure of paramyxoviruses can be found in [ 37 , 46 , 47 ].…”

Structural landscape of the Respiratory Syncytial Virus nucleocapsids

“…Similarly to other Mononegavirales 20,21 , the N-and C-terminal extensions of RSV N, termed NTD-arm (residues 1-36) and CTD-arm (residues 360-391) (Figure 1h), interact with the laterally adjacent N protomers thereby stabilising their oligomeric assembly on the RNA strand by subdomain swapping (Figure 2a). The visible part of the CTD-arm of Ni lies on top of the CTD of Ni+1 implying that in a helical NC it should be situated in between consecutive turns 4 .…”