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WARF: P01273US

Replicating Influenza Mutants with Reduced Sialidase Activity


INVENTORS -

Yoshihiro Kawaoka

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing mutant host cells that can be used to propagate influenza A virus mutants with reduced sialidase activity.
OVERVIEWInfluenza A virus possesses two surface spike proteins, hemagglutinin (HA) and neuraminidase (NA). HA binds to sialic acid-containing receptors on host cell surfaces.  NA cleaves terminal sialic acid residues from the glycoconjugates of host cells, which is necessary for the efficient release of progeny virions.  Thus, the receptor-binding activity of HA and the receptor-destroying activity of NA counterbalance each other to allow efficient replication of influenza virus.

Because sialic acid plays a key role in the influenza virus life cycle, influenza viruses with reduced sialidase activity could be useful for vaccine development or gene delivery.  Altered host cells are needed to propagate such viruses.
THE INVENTIONA UW-Madison researcher has developed mutant cells useful for propagating influenza A virus mutants with reduced sialidase activity. The mutant cells have decreased levels of sialic acid and sialic acid-containing cell receptors as compared to wild type cells.

To generate the mutant cells, the researcher started with cells that supported the growth of influenza virus. These cells were incubated with a growth-inhibiting agent. Surviving cell colonies were cloned and infected with influenza virus variants with known sialic acid receptor-linkage specificity. A small percentage of cells, designated as MaKS cells, continued to grow without any evidence of virus production, and showed lowered levels of sialic acid-containing receptors. Two influenza virus variants that were able to grow well in these cells after several rounds of selection showed large deletions in the gene for NA as compared to the parent viruses.
APPLICATIONS
  • Increasing our understanding of how influenza A viruses adapt to new environments and infect new hosts
  • Expanding influenza viral vectors for commercial use
  • Developing influenza virus vaccines
  • Propagating influenza viruses with reduced sialidase activity
KEY BENEFITS
  • Mutant host cells are resistant to growth inhibition by a lectin that binds terminal sialic acid residues.
  • MaKS cells may be useful in viral receptor-based analyses.
ADDITIONAL INFORMATION
For More Information About the Inventors
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Contact Information
For current licensing status, please contact Jennifer Gottwald at jennifer@warf.org or 608-960-9854.
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