Differential Localization and Function of PB1-F2 Derived from Different Strains of Influenza A Virus
| Autor: | Chi-Jene Chen, Yeau-Ching Wang, Chih-Heng Huang, Guang-Wu Chen, Ching-Ho Wang, Shin-Ru Shih |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
animal structures
Genes Viral Swine Viral protein viruses Molecular Sequence Data Immunology Orthomyxoviridae Influenza A Virus H7N7 Subtype Apoptosis Transfection Virus Replication medicine.disease_cause Microbiology Virus Cell Line Birds Mice Viral Proteins Influenza A Virus H1N1 Subtype Species Specificity Virology medicine Influenza A virus Animals Humans Amino Acid Sequence Gene Peptide sequence Genetics Mice Inbred BALB C Mutation Influenza A Virus H5N1 Subtype Sequence Homology Amino Acid Virulence biology Genetic Variation virus diseases biochemical phenomena metabolism and nutrition biology.organism_classification Recombinant Proteins Influenza A virus subtype H5N1 Virus-Cell Interactions Insect Science Female HeLa Cells |
| Zdroj: | Journal of Virology. 84:10051-10062 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.00592-10 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|