influenza virus polymerase (FluPol)

The influenza virus polymerase (FluPol) is implicated in both (i) transcription and (ii) replication of the viral RNA (vRNA). Replication allows to generate new viral genome copies (vRNA) through the synthesis of a complementary RNA (cRNA). The ability of avian influenza virus to efficiently replicate in human cells is mediated by a mechanism of host adaptation, i.e key mutations on the PB2 subunit of FluPol, together with the hijacking of the host factor ANP32, whose sequence differs between avian and human species. Several studies are also suggesting another role for ANP32 which is to act during the cRNA to vRNA replication step by recruiting a second polymerase that would encapsidate the nascent 5’ vRNA extremity. Using cryo-EM, we aim to decipher the mechanistic details of the interaction between FluPol and ANP32 in order to better understand (i) the function of ANP32 during the replication cycle of influenza virus and (ii) host range restriction of influenza virus.