Abstract
Influenza A viruses of the H1N1 and H3N2 subtypes are responsible for seasonal epidemic events. The influenza nucleoprotein (NP) binds to the viral genomic RNA and is essential for its replication. Efforts are under way to produce therapeutics and vaccines targeting the NP. Despite this, no structure of an NP from an H3N2 virus has previously been determined. Here, the structure of the A/Northern Territory/60/1968 (H3N2) influenza virus NP is presented at 2.2 Å resolution. The structure is highly similar to those of the A/WSN/1933 (H1N1) and A/Hong Kong/483/97 (H5N1) NPs. Nonconserved amino acids are widely dispersed both at the sequence and structural levels. A movement of the 73-90 RNA-binding loop is observed to be the key difference between the structure determined here and previous structures. The data presented here increase the understanding of structural conservation amongst influenza NPs and may aid in the design of universal interventions against influenza.
Highlights
Influenza A viruses (IAVs) make a large contribution to the seasonal influenza burden and have established pandemic potential
Each segment is assembled into a ribonucleoprotein complex, with the 50 and 30 termini both bound by the trimeric influenza virus polymerase
We present the structure of the NP from the A/Northern Territory/60/1968 (H3N2) influenza virus (NT60) and discuss how it differs from previously determined influenza virus NP structures
Summary
Influenza A viruses (IAVs) make a large contribution to the seasonal influenza burden and have established pandemic potential. The major antigenic components of IAVs are the hemagglutinin and neuraminidase proteins that decorate the viral envelope. Structures have been determined of NPs from influenza A, B (Ng et al, 2012) and D (Donchet et al, 2019) viruses. Mutational analysis and structural information suggest that RNA binding is mediated by a basic groove located between the head and body domains (Ye et al, 2006; Elton et al, 1999). This basic groove is thought to associate with the phosphate backbone of the RNA. We present the structure of the NP from the A/Northern Territory/60/1968 (H3N2) influenza virus (NT60) and discuss how it differs from previously determined influenza virus NP structures
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