With hospitalizations estimated in the hundreds of thousands for influenza, research is more important than ever.

Researchers at the Biocomplexity Institute of Virginia Tech’s Nutritional Immunology and Molecular Medicine Laboratory (NIMML) have recently explored a new therapeutic target to treat flu infection.

The work, published in Frontiers in Immunology, characterizes the effects of lanthionine synthetase C-like 2 (LANCL2) to target influenza A infection in mice. LANCL2 is a therapeutic target for inflammatory and autoimmune diseases.

While vaccines have been valuable against the spread of infections, they often require more than 6 months from the emergence of a particular strain to become fully developed. In contrast, the current option for those contracting disease, is an anti-viral treatment such as Tamiflu.

Unlike vaccines, numerous issues arise with current anti-viral treatments, such as the need for administration immediately after first presentation of symptoms or the potential for emergence of resistant strains. Current treatments are modestly successful since they only amount to only a 24-hour reduction in the disease.

Anti-virals used to treat influenza such as Tamiflu target the virus rather than the immune response to the virus,” said Josep Bassaganya-Riera, the NIMML Director. “We provide novel evidence that modulating the host response to influenza virus by activating LANCL2 can dramatically ameliorate survival, disease and pathology during influenza and possibly outperform Tamiflu, the current standard of care for treating infections with influenza virus.”

When compared to Tamiflu, activating the drug LANCL2 in mice results in increased survival and accelerated recovery from influenza.

“The combined observation that the genetic loss of LANCL2 and the pharmacological activation of LANCL2 through a small molecule both impact the overall disease response during influenza but in opposite patterns is strong validation that LANCL2 is an important target in the control of general immune responses and potentially specifically within responses to viral pathogens,” said Andrew Leber, NIMML Ph.D student in Genetics, Bioinformatics, and Computational Biology.

The NIMML researchers in 2013 demonstrated the natural ligand of LANCL2, abscisic acid (ABA), ameliorates influenza in mice. Those findings were published in the Journal of Nutritional Biochemistry.

“While the immune effects of LANCL2 are well understood in the gastrointestinal (GI) tract, less was known about what this receptor does in the respiratory tract. We have shown conclusively that not only does LANCL2 activation ameliorate disease activity and lung inflammatory pathology, it does it through a mechanism involving upregulation of lung IL-10, a potent anti-inflammatory protein, in influenza-infected mice,” said Raquel Hontecillas, co-Director of NIMML and the corresponding author of the paper.

Given the risk of developing resistance to current anti-viral remedies as Tamiflu, future studies need to explore utilizing the next generation of LANCL2-based host-targeted therapeutics against influenza.

Published by Becky Freemal, April 06, 2017
Tags: Disease  Flu  Precision Medicine