18 Jan 2016

Publication: promising therapeutic target to reduce Influenza A viruses infection

On January 8, 2016, Chris Mok - principal investigator at HKU-Pasteur Research Pole - and co-workers published a study in the American Journal of Physiology - Lung Cellular and Molecular Physiology: "Targeting host calpain proteases decreases influenza A virus infection". This research was a collaboration led by Mustapha Si-Tahar (Research Centre for Respiratory Diseases, Inserm, Université de Tours) and conducted between Institut Pasteur Paris, Université Paris 6, Inserm (French National Institute of Health and Medical Research), Hong Kong University and HKU-Pasteur Research Pole.

The development of new strategies aiming at reducing the severity of Influenza A viruses is still a major public health challenge today. Vaccines and antiviral drugs are available, yet treatment of influenza faces limitations. Vaccines have reduced immunogenicity and efficacy in high-risk populations (elderly and immunocompromized individuals), the constant antigenic drift requires annual updating of the vaccine, and antiviral drugs do not interfere with immunopathology. Thus, looking for innovative therapies targeting host cellular molecules and not only viral factors can broaden and improve the efficiency of the therapeutic arsenal of influenza.

Such molecules could include the calpains, ubiquitous calcium-dependent proteases. This study provides new insight into the role of this protein family in influenza A viruses pathogenesis and shows that targeting calpains-dependent signaling pathways with calpain inhibitors has a protective effect in influenza A viruses infection, reduces viral replication, leukocyte infiltration and expression of pro-inflammatory mediators in bronchial epithelial cells. Regarding the treatment of influenza-induced acute pneumonia, this novel approach targeting calpains could then offer a new therapeutic option.

"Hyperactivation of the immune system observed in patients is considered as one of the mechanisms of the pathogenicity of avian influenza virus (H5N1) infection. The discovery of using calpain inhibitor, a potent inflammation inhibitor, could pave the way to a new therapeutic strategy for the treatment of H5N1 disease" sumarizes Chris Mok.