The PB2 subunit of the influenza virus RNA polymerase is a major determinant of viral pathogenicity. The molecular mechanisms of how PB2 determines pathogenicity remain poorly understood. PB2 is responsible for binding to the 5΄ cap of nascent host pre-mRNAs to facilitate cleavage by PA into short capped RNA fragments, which are used as primers for viral transcription. Meanwhile, PB2 has been implicated in virulence and host adaptation. PB2 associates with mitochondria and inhibits the function of the mitochondrial antiviral signaling protein MAVS, implicating PB2 in the regulation of innate immune responses.
Polymerase basic 2 / PB2 cDNAs
PB2 is an 87-kDa basic cap-binding protein involved in the initiation of viral transcription as well as viral replication. The N- and C-terminal egions of PB2 contain independent NP binding sites, located between residues 1–269 and 580–683, respectively. The interaction of PB2 with NP affected the activity of RNPs, and may be involved in regulating the switch from viral transcription to replication. Two regions of PB2 (aa 448–496 and aa 736–739) were required for the nuclear localization of influenza virus PB2.
An N-terminal mitochondrial targeting sequence (MTS) was found to be responsible for the mitochondrial localization of PB2. Despite high sequence conservation in this region, position 9 shows variations in influenza A viruses of different hosts and is a determinant of the mitochondrial localization of PB2. Most human seasonal influenza virus pre-2009 H1N1, H2N2, and H3N2 strains encode mitochondrial PB2 with asparagine at position 9 (N9-PB2).
Polymerase basic 2 (PB2) protein is a component of the influenza A virus RNA-dependent RNA polymerase complex alongside the polymerase basic 1 (PB1) and polymerase acidic (PA) protein subunits. PB2 associates with mitochondria and inhibits the function of the mitochondrial antiviral signaling protein MAVS. PB2 of some influenza virus strains has also been found to localize to the mitochondria, independentlyf PB1 and PA.
PB2 has been implicated in virulence and host adaptation. Several residues in PB2 have been found to be important for host adaptation.
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