RNA structure interactions and ribonucleoprotein processes of the influenza A virus

Dawson, Wayne K; Lazniewski, Michal; Plewczynski, Dariusz

In forming the viral cRNA, the NP coating is either somehow removed or used with the polymerase heterotrimer to produce the cRNA transcript, where the cRNA is assembled into a RNP (cRNA with the polymerase and scaffold of NPs) that is the template used to replicate the negative-strand sequence (ccRNA; the new copy of vRNA). Both cRNA and ccRNA bind the viral polymerase heterotrimer (PA-PB1-PB2). Hence, cRNA and ccRNA have the NP complex coating onto which the newly synthesized polymerase heterotrimer can bind. As both cRNA and its replication product ccRNA bind the viral polymerase, nuclear export requires a way to distinguish between them and export only the replicated vRNPs. The apparent factor determining this is the binding of M1 to the vRNPs, and not the cRNPs [31, 76] . The export of the newly created vRNPs is further mediated by NEP that directly interacts with NEPs CRM1 (chromosomal maintenance 1, also known as exportin 1) [19, 51, 79] , where NEP may enlarge the nuclear pores [80] . Somewhere during the transit (in the cytosol) or somewhere near the point where the individual vRNPs arrive at the cellular membrane, the vRNPs manage to group into the eight segments that form the genome in the 7 þ 1 pattern [46] . The selective aggregation of the vRNPs may be because of mutual interactions, proteins factors or RNA-RNA interactions [81] , where the latter appears to have some support (see next section). However, the precise secondary structure and the interactions between neighboring vRNPs are unknown.