Influenza (flu) is a highly contagious respiratory illness that affects millions of people each year and poses a continuous threat to public health. In particular, the emergence of a new influenza A virus for which there is little or no immunity in the human population may provoke an influenza pandemic, similar to that of the Spanish flu in 1918.
Currently available measures for the control of influenza in humans are vaccination and antiviral medications, which target the viral neuraminidase NA or the M2 protein. But treatment options are challenged due to the development of drug-resistant viruses for both M2 and NA inhibitors and furthermore the production of influenza vaccines against a newly emerged virus requires 4–6 months, highlighting the urgent need for novel drug targets.
Leading experts in the field Eva Böttcher-Friebertshäuser, Hans-Dieter Klenk and Wolfgang Garten of the Institute of Virology, Philipps-University Marburg present a timely, authoritative review published in FEMS Pathogens and Disease on the proteolytic cleavage of the influenza hemagglutinin (HA), an activation mechanism that is essential for the infectivity of influenza viruses, including the recently emerged H7N9 that will be of considerable interest to virologists, microbiologists and pharmaceutical companies alike.
Interestingly, certain bacteria have been demonstrated to support HA activation either by secreting proteases that cleave HA or due to activation of cellular proteases and thereby may contribute to virus spread and enhanced pathogenicity. As a result, viral-bacterial pneumonia and secondary bacterial pneumonia due to concomitant or subsequent infection with bacteria, respectively, contribute significantly to morbidity and mortality of influenza infections.
HA-activating proteases have been shown to represent potential drug targets for influenza treatment. The authors suggest that the combination of appropriate protease inhibitors with current antivirals and/or antimicrobial drugs provide a novel and promising approach that should be considered for the treatment of both influenza and viral-bacterial pneumonia. /Gillian van Beest
Böttcher-Friebertshäuser, E. et al., Activation of influenza viruses by proteases from host cells and bacteria in the human airway epithelium. FEMS Pathogens and Disease 2013.