Influenza A virus polymerase basic protein 2 (PB2)

Influenza A virus polymerase basic protein 2 (PB2) is a vital subunit of the heterotrimeric RNA-dependent RNA polymerase (RdRp) complex, which also includes PB1 and PA (UniProt P03433). PB2 is responsible for the 'cap-snatching' mechanism, specifically binding the 5' cap of host pre-mRNAs to initiate viral mRNA synthesis (PubMed: 25143583). It serves as a key determinant of host-cell adaptation and viral pathogenicity, with specific residues like 627 and 701 influencing the ability of avian viruses to replicate in mammalian cells (PubMed: 11160720). Due to its high sequence conservation across diverse influenza A subtypes, PB2 contains critical T-cell epitopes that are targeted in the development of universal influenza vaccines to induce cross-protective cellular immunity (PubMed: 29335241). Furthermore, the PB2 cap-binding site is the target of the antiviral drug pimodivir (VX-787), which inhibits viral replication by blocking the transcription initiation process (PubMed: 27903808).

Other names

Polymerase basic protein 2PB2 subunitRNA-directed RNA polymerase subunit PB2Host-range determinant PB2PB2 conserved T-cell epitopes

Pimodivir acts as a first-in-class inhibitor that binds to the 7-methylguanosine (m7G) cap-binding pocket of the PB2 subunit, preventing the virus from acquiring host-derived primers necessary for viral mRNA transcription (PubMed: 24297900).