The polymerase basic protein 1 (PB1) gene of pandemic H1N1

The second genomic segment of the influenza A virus encodes the polymerase basic protein 1 gene (PB1). This is the second longest genomic segment and is sometimes labeled “segment 2”. This gene produces three proteins: PB1 (sometimes referred to as PB-F1), PB1-F2 and N40.

When the BLAST program is used to align A/California/04/2009(H1N1) PB1 with sequences from GenBank, the nucleotide sequence was most similar to A/Wisconsin/10/98 (H1N1) – 96% identical. This strain was apparently isolated from a man in Wisconsin in 1998. The best protein match for A/California/04/2009(H1N1) PB1 was also A/Wisconsin/10/98 (H1N1). However, several isolates from North American birds had an identical protein sequence to A/Wisconsin/10/98 (H1N1), including: A/northern pintail/South Dakota/Sg-00126/2007(H3N2), A/mallard/South Dakota/Sg-00127/2007, A/mallard/South Dakota/Sg-00128/2007(H3N2), A/mallard/South Dakota/Sg-00125/2007(H3N2). The PB1 protein from A/California/04/2009(H1N1) was 98% identical to A/Wisconsin/10/98 (H1N1) and the four avian virus proteins.

The PB1 subunit works with PB2 and PA subunits to create the viral polymerase. This polymerase is responsible for the transcription and replication of the viral genome.

N40 is a newly described protein of influenza A virus from the PB1 gene (Wise et al., 2009). It does not appear to be necessary for replication, but failure to produce it appears to impair the replication, under certain conditions.

PB1-F2 is unusual in that this protein is coded by a subset of the nucleotides that code for PB1. This is due to the use of a different reading frame (+1). Thus, the PB1 and PB1-F2 proteins are completely different in sequence (Lamb and Takeda, 2001; Chen et al. 2001). They also appear to be completely different in function. While PB1 is involved transcription and replication, PB1-F2 may play a role in the virulence of influenza strains (Zamarin et al. 2006). PB1-F2 has been implicated in the severe symptoms and high death rate associated with the 1918 virus (Kash, et al. 2006). PB1-F2 is thought to kill cells by interfering with the function of mitochondria. These organelles are the energy power plants of cells. If these structures fail, a cell will die. It has been suggested that PB1-F2 is especially lethal to immune system cells (Chen et al. 2001).

The 2009 pandemic influenza H1N1 does not produce a full length PB1-F2 protein. The new H1N1 virus PB1 gene codes for an 11 amino acid peptide instead of a 90 amino acid protein for PB1-F2 due to mutations which create stop codons (Ramakrishnan, 2009, Trifonov et al. 2009). Thus, a few nucleotide mutations in the pandemic H1N1 PB1 gene could create a functioning PB1-F2 protein. This, in turn, might cause an instant increase in the lethality of this virus.

References

Wise et al. (2009) A Complicated Message: Identification of a Novel PB1-Related Protein Translated from Influenza A Virus Segment 2 mRNA. J. Virol. 83: 8021-8031.

Trifonov et al. (2009) The contribution of the PB1-F2 protein to the fitness of influenza A viruses and its recent evolution in the 2009 influenza A (H1N1) pandemic virus. PLoS Currents: Influenza. 2009;22

Ramakrishnan (2009) A Serine12Stop mutation in PB1-F2 of the 2009 pandemic (H1N1) influenza A: a possible reason for its enhanced transmission and pathogenicity to humans. J. Vet. Sci. 10: 349-351

Wanitchang et al. (2009) Enhancement of reverse genetics-derived swine-origin H1N1 influenza virus seed vaccine growth by inclusion of indigenous polymerase PB1 protein. Virus Res. Oct. 30.

Conenello et al. (2007) A Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence. PLoS Pathogens. 3: e141.

Zamarin et al. (2006) Influenza A Virus PB1-F2 Protein Contributes to Viral Pathogenesis in Mice. J Virol. 80: 7976–7983.

Kash et al. (2006) Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus. Nature. 443: 578–581.

Obenauer et al. (2006) Large-scale sequence analysis of avian influenza isolates. Science. 311:1576-80.

Holmes (2006) Comment on “Large-Scale Sequence Analysis of Avian Influenza Isolates”. Science. 313: 1573.

Zamarin et al. (2005) Influenza Virus PB1-F2 Protein Induces Cell Death through Mitochondrial ANT3 and VDAC. PLoS Pathog. 1: e4

Chen et al. (2001) A novel influenza A virus mitochondrial protein that induces cell death. Nature Medicine. 7: 1306 – 1312.

Lamb and Takeda (2001) Death by influenza virus protein. Nature Medicine 7, 1286 – 1288.

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2 Comments

Filed under Science

2 responses to “The polymerase basic protein 1 (PB1) gene of pandemic H1N1

  1. deanb2001

    Thanks for the lessons, Monotreme. Keep’em comin’.

  2. monotreme1000

    Thanks, deanb. 2 down, 6 to go.

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