Abstract
Non-segmented negative-strand RNA viruses, such as measles, ebola and Newcastle disease viruses (NDV), encapsidate viral genomic RNAs into helical nucleocapsids, which serve as the template for viral replication and transcription. Here, the clam-shaped nucleocapsid structure, where the NDV viral genome is sequestered, was determined at 4.8 Å resolution by cryo-electron microscopy. The clam-shaped structure is composed of two single-turn spirals packed in a back-to-back mode. This tightly packed structure functions as a seed for the assembly of a nucleocapsid from both directions, facilitating the growth of double-headed filaments with two separate RNA strings inside. Disruption of this structure by mutations in its loop interface yielded a single-headed unfunctional filament.
Highlights
Members of the order Mononegavirales encompass some of the most lethal human and animal pathogens, including ebola, rabies virus, measles, nipah virus and the human respiratory syncytial virus (RSV) (Amarasinghe et al, 2017; Kuhn et al, 2010)
Under negative-stain EM, purified N exhibited round-shaped structures with a small portion of doubleheaded filaments of different lengths (Figure 1—figure supplement 1B), which are similar to the nucleocapsids of measles that are expressed in Sf21 insect cells (Jensen et al, 2011), of sendai virus in mammalian cells (Buchholz et al, 1993) and of hendra virus in E. coli (Communie et al, 2013)
Homolog modeling on Newcastle disease virus (NDV) N, based on the 40% sequence identity of N between NDV and Parainfluenza virus 5 (PIV5) (Alayyoubi et al, 2015), resulted the subunit N model and the model was flexibly docked into the EM density map (Figure 1C, Figure 1—figure supplement 3A,B)
Summary
Members of the order Mononegavirales encompass some of the most lethal human and animal pathogens, including ebola, rabies virus, measles, nipah virus and the human respiratory syncytial virus (RSV) (Amarasinghe et al, 2017; Kuhn et al, 2010). During viral RNA synthesis, the assembled nucleocapsid, rather than the naked RNA genome, is opened and unveiled so that it can be recognized by the viral RNA-dependent RNA polymerase (RdRp) and it serves as the template for both replication and transcription In RNP oligomers, the NTD and CTD interact successively with adjacent N proteins, forming long helical filaments that efficiently protect the viral genome, and which serve as the template for viral RNA transcription and the replication of new virions (Ge et al, 2010; Zhou et al, 2013). The Newcastle disease virus (NDV), a member of the genus Avulavirus, family Paramyxoviridae, which is relatively safe for handling, was selected as the model to look at how NDV RNP protects its viral genome and to provide new insights into the development of nucleocapsidbased antivirus therapies
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