Mutations in matrix protein 1 and nucleoprotein caused human-specific defects in nuclear exportation and viral assembly of an avian influenza H7N1 virus.

Nuclear exportation of influenza ribonucleoprotein is a vital step in viral replication cycle. In this study a particular H7N1 (A/ostrich/Zimbabwe/222-E3/1996) virus showed exclusively nuclear localization of the viral nucleoprotein (NP) only in human cell lines but not in cell lines of other species suggesting a human-specific nuclear exportation defect. After 10 passages in human lung cells, an adapted strain (H7N1:P10) could efficiently replicate and export viral NP in human cells. Mutations in the NP and matrix M1 gene at position 297 and 227, respectively, were found to rescue the defect. While the NP mutant showed a comparable ratio of total to NP-associated negative-sense RNA in the cytoplasm as compared to the wild type, the M1 mutant showed an increase in free negative-sense RNA in the cytoplasm. These indicated that the NP mutation might cause a nuclear export defect, whereas the M1 mutation might cause a defect in ribonucleoprotein assembly step.

Evolutionary dynamic of antigenic residues on influenza B hemagglutinin.

Hemagglutinin (HA) of seasonal influenza virus evolves under positive selection pressure exerted by host immunity. It was previously shown that antigenic drift in different influenza B sublineages during different time periods distributed unevenly among different epitopes, and that more recent viruses up to 2007 might have their antigenic drift more focused on certain epitope. We further analyzed whether more recent influenza B viruses up to 2016 followed that same pattern of antigenic evolution. By using Shannon entropy and relative entropy to characterize HA antigenic epitopes, the most recent viruses of both Victoria and Yamagata lineages had residues with high relative entropy located most frequently on the 120-loop region. In addition to residues in the known epitopes, possible antigenic residues were also identified outside of the known epitope regions. The data provide an insight into the antigenic evolution of current influenza B viruses and expand our knowledge on their antigenic sites.

Expression of importin-α isoforms in human nasal mucosa: implication for adaptation of avian influenza A viruses to human host.

BACKGROUND: Transportation into the host cell nucleus is crucial for replication and transcription of influenza virus. The classical nuclear import is regulated by specific cellular factor, importin-α. Seven isoforms of importin-α have been identified in human. The preference of importin-α3 of avian influenza virus and -α7 isoform of human strains during replication in human cells was previously identified. In addition, both avian and human influenza viruses were shown to use importin-α1 isoform for their replication. FINDING: The mRNA levels of importin-α1, -α3, and -α7 isoforms in human respiratory tract was determined by real-time RT-PCR. The results indicate that mRNA level of importin-α7 was significantly higher than that of importin-α1 (p-value < 0.0001) and importin-α3 (p-value < 0.0001) isoforms in human nasal mucosa while importin-α1 was detected as the highest expression importin-α isoform in lung tissues. CONCLUSIONS: These results may explain the preference of importin-α7 isoforms in seasonal influenza viruses in human upper respiratory tract and may suggest a selective pressure toward importin-α7 in human respiratory tract infection of an avian virus.