Abstract
Influenza A virus controls replication and transcription of its genome through the tight regulation of interaction between the ribonucleoprotein (RNP) complex subunits. The helical scaffold of RNP is maintained by nucleoprotein (NP). Previous studies have revealed that NP interacts with both PB2 N-terminal and C-terminal regions, with both regions sharing similar affinity to NP as revealed in co-immunoprecipitation assay. Our work here suggests that the interaction between NP and PB2 N-terminal region lies in the cap-binding domain (residue 320–483). By co-immunoprecipitation assay, the interaction was found to involve RNA. On the other hand, the cap-binding activity was not essential in the interaction. As shown by the NHS pull-down assay, a specific RNA sequence was not required. Among the cap-binding domain, residues K331 and R332 of PB2 play a role in RNP function so that polymerase activity was reduced when these residues were mutated, while K331 was found to be more crucial in the NP interaction. Collectively, our findings suggest a new binding mode between NP and PB2 which was mediated by RNA, and such interaction may provide a novel interacting site for influenza drug development.
Highlights
Influenza virus is one of the major causes of contagious respiratory disease
Genome of influenza A virus consists eight segments of single stranded, negative sense viral RNA which is packaged into a rod-shape viral ribonucleoprotein complex scaffold [1,2,3]
The current study reveals a novel interaction between NP and PB2 cap-binding domain
Summary
Influenza virus is one of the major causes of contagious respiratory disease. Annual influenza epidemics can claim up to 650,000 lives every year, causing a heavy burden to the healthcare system. Genome of influenza A virus consists eight segments of single stranded, negative sense viral RNA (vRNA) which is packaged into a rod-shape viral ribonucleoprotein (vRNP) complex scaffold [1,2,3]. This complex is assembled by multiple nucleoproteins (NPs) and a heterotrimeric RNA-dependent RNA polymerase (RdRP). NP oligomer is arranged in a double helical conformation to coat vRNA while the RdRP binds the 3’ and 5’ termini of the vRNA [1, 2, 5]
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