Polymerase basic protein 2 subunit of influenza A virus (PB2)

Polymerase basic protein 2 (PB2) is a key subunit of the influenza A virus heterotrimeric RNA-dependent RNA polymerase complex, which consists of PB2, PB1, and PA. PB2 is primarily responsible for recognizing and binding the 5′ cap of host pre-mRNA transcripts, a prerequisite step for "cap-snatching"—where short host-capped RNA fragments are used to prime viral mRNA synthesis. PB2 is also involved in the interface with PB1, regulating overall polymerase activity and complex formation essential for virus replication. Mutations in PB2, particularly within its 627 domain and its mitochondrial targeting sequence, are critical for host adaptation, influencing both the efficiency of viral replication and pathogenicity in humans versus avian hosts. PB2's unique structural conservation and central catalytic functions have made it a prime target for antiviral drug development. Besides its canonical nuclear function, mitochondrial localization of PB2 has been implicated in the regulation of cell death and dampening of innate immune responses, providing additional routes by which influenza A manipulates host defenses.

Other names

PB2Polymerase basic protein 2Influenza A virus PB2

Inhibition of cap-binding or polymerase activity Interference with PB1–PB2 interaction Inhibition of RNA synthesis