Nucleocapsid Structure of Negative Strand RNA Virus

Abstract

Negative strand RNA viruses (NSVs) include many important human pathogens, such as influenza virus, Ebola virus, and rabies virus. One of the unique characteristics that NSVs share is the assembly of the nucleocapsid and its role in viral RNA synthesis. In NSVs, the single strand RNA genome is encapsidated in the linear nucleocapsid throughout the viral replication cycle. Subunits of the nucleocapsid protein are parallelly aligned along the RNA genome that is sandwiched between two domains composed of conserved helix motifs. The viral RNA-dependent-RNA polymerase (vRdRp) must recognize the protein–RNA complex of the nucleocapsid and unveil the protected genomic RNA in order to initiate viral RNA synthesis. In addition, vRdRp must continuously translocate along the protein–RNA complex during elongation in viral RNA synthesis. This unique mechanism of viral RNA synthesis suggests that the nucleocapsid may play a regulatory role during NSV replication.

Structural insights into RNA polymerases of negative-sense RNA viruses

“…The genome of NSVs consists of one or more single-stranded, negative-sense RNA molecules that are assembled with multiple copies of viral nucleoprotein into megadalton-sized viral ribonucleoprotein (vRNP) complexes with a helical configuration 1 (Box 1 ). The nucleoproteins are the main determinants of this helical configuration and oligomerize to form a scaffold for the genomic viral RNA (vRNA).…”

“…The nucleoproteins are the main determinants of this helical configuration and oligomerize to form a scaffold for the genomic viral RNA (vRNA). In non-segmented NSVs (nsNSV), these vRNP structures are highly symmetrical and relatively rigid 1 , 2 . In segmented NSVs (sNSVs), each individual segment is contained in a distinct vRNP complex that is relatively flexible 3 , 4 .…”

Characterization of SARS-CoV-2 N protein reveals multiple functional consequences of the C-terminal domain

“…Previous studies, including our own, have examined fundamental properties of nucleocapsid or nucleoproteins (N) from RNA viruses, which revealed overlapping and unique functions (Arragain et al, 2019; Ding et al, 2016; Lu et al, 2020; Luo et al, 2020; Raymond et al, 2010; Su et al, 2018; Wan et al, 2017). These include the insights into RNA binding, oligomerization, as well as potential roles in RNA synthesis and immune evasion.…”

RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic

“…Consequently, this dsRNA routes the development of brand-new viral RNA. The genome of negative-sense ssRNA viruses must be copied by an RNA replicase to form positive-sense RNA [ 21 , 22 ]. The positive-sense RNA molecule then acts as viral mRNA, and this mRNA is translated into proteins by host ribosomes.…”