Differential localization and function of PB1-F2 derived from different strains of influenza A virus.
PB1-F2 is a viral protein that is encoded by the PB1 gene of influenza A virus by alternative translation. It varies in length and sequence context among different strains. The present study examines the functions of PB1-F2 proteins derived from various human and avian viruses. While H1N1 PB1-F2 was found to target mitochondria and enhance apoptosis, H5N1 PB1-F2, surprisingly, did not localize specifically to mitochondria and displayed no ability to enhance apoptosis. Introducing Leu into positions 69 (Q69L) and 75 (H75L) in the C terminus of H5N1 PB1-F2 drove 40.7% of the protein to localize to mitochondria compared with the level of mitochondrial localization of wild-type H5N1 PB1-F2, suggesting that a Leu-rich sequence in the C terminus is important for targeting of mitochondria. However, H5N1 PB1-F2 contributes to viral RNP activity, which is responsible for viral RNA replication. Lastly, although the swine-origin influenza virus (S-OIV) contained a truncated form of PB1-F2 (12 amino acids [aa]), potential mutation in the future may enable it to contain a full-length product. Therefore, the functions of this putative S-OIV PB1-F2 (87 aa) were also investigated. Although this PB1-F2 from the mutated S-OIV shares only 54% amino acid sequence identity with that of seasonal H1N1 virus, it also increased viral RNP activity. The plaque size and growth curve of the viruses with and without S-OIV PB1-F2 differed greatly. The PB1-F2 protein has various lengths, amino acid sequences, cellular localizations, and functions in different strains, which result in strain-specific pathogenicity. Such genetic and functional diversities make it flexible and adaptable in maintaining the optimal replication efficiency and virulence for various strains of influenza A virus.
Chen
Chi-Jene
CJ
Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, Republic of China.
Chen
Guang-Wu
GW
Wang
Ching-Ho
CH
Huang
Chih-Heng
CH
Wang
Yeau-Ching
YC
Shih
Shin-Ru
SR
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001717:Birds / Q000821:virology; D002460:Cell Line; D005260:Female; D005814:Genes, Viral; D014644:Genetic Variation; D006367:HeLa Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D053126:Influenza A Virus, H7N7 Subtype / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D009980:Influenza A virus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013552:Swine / Q000821:virology; D014162:Transfection; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014774:Virulence / Q000502:physiology; D014779:Virus Replication / Q000502:physiology
C442816:PB1-F2 protein, Influenza A virus; D011994:Recombinant Proteins; D014764:Viral Proteins