International Journal of Medical Microbiology 304 (2014) 894–901 Contents lists available at ScienceDirect International Journal of Medical Microbiology j ourna l ho me page: www.elsevier.com/locate/ijmm Mini Review Influenza, a One Health paradigm—Novel therapeutic strategies to fight a zoonotic pathogen with pandemic potential Stephan Ludwig a,* , Roland Zell b , Martin Schwemmle c , Susanne Herold d a Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany b Department of Virology and Antiviral Therapy, Jena University Hospital, Friedrich Schiller University Jena, Hans Knoell Str. 2, D-07745 Jena, Germany c Institute for Virology, University Medical Center Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany d Universities Giessen & Marburg Lung Center (UGMLC), Department of Internal Medicine II, Section of Infectious Diseases, Klinikstr. 33, D-35392 Giessen, Germany a r t i c l e i n f o Keywords: Influenza virus Antiviral therapy Signal transduction Immune modulation Polymerase complex One Health a b s t r a c t Influenza virus is a paradigm for a pathogen that frequently crosses the species barrier from animals to humans, causing severe disease in the human population. This ranges from frequent epidemics to occasional pandemic outbreaks with millions of death. All previous pandemics in humans were caused by animal viruses or virus reassortants carrying animal virus genes, underlining that the fight against influenza requires a One Health approach integrating human and veterinary medicine. Furthermore, the fundamental question of what enables a flu pathogen to jump from animals to humans can only be tackled in a transdisciplinary approach between virologists, immunologists and cell biologists. To address this need the German FluResearchNet was established as a first nationwide influenza research network that virtually integrates all national expertise in the field of influenza to unravel viral and host determinants of pathogenicity and species transmission and to explore novel avenues of antiviral intervention. Here we focus on the various novel anti-flu approaches that were developed as part of the FluResearchNet activities. © 2014 Elsevier GmbH. All rights reserved. Introduction Influenza is a prime example of a zoonotic disease and high- lights the relevance of a One Health approach, where experts in animal and human health-care and research combine their efforts to solve interrelated problems. Human disease due to pan- demic (H1N1) 2009 influenza and avian to human transmission of influenza A/H5N1or A/H7N9 viruses are only recent examples of new zoonoses with significant global impact. Management, pre- vention and treatment of influenza requires the expansion and continuing support of collaborations between human and animal health experts at the clinical, diagnostic laboratory, public health, research and training levels. Influenza A/H5N1, first isolated in 1996 from a goose in Guang- dong province in China, caused severe poultry losses and occasional human infections in Hong Kong in 1997 (Watanabe et al., 2012). The main human public health response that controlled this outbreak was an aggressive poultry cull. However, from 2003 the * Corresponding author. Tel.: +49 251 835 7791; fax: +49 251 835 7793. E-mail address: ludwigs@uni-muenster.de (S. Ludwig). virus continued to spread to different other parts of the world. Since then, more than 600 sporadic cases of human infection with influenza A/H5N1 viruses with high lethality have been reported, primarily by 15 countries in Asia, Africa, the Pacific, Europe and the Near East (Watanabe et al., 2012). In January 2014, the first case of a human infection with H5N1 in the Americas was reported from Canada. Fortunately, human-to-human transmission of H5N1 was and is still rare, so far preventing pandemic spread of this potentially devastating pathogen. Human infections with a new avian H7N9 virus were first reported in China in March 2013 (Liu et al., 2014). Most of these infections are believed to result from exposure to infected poul- try or contaminated environments, as H7N9 viruses have also been found in poultry in China. Most patients have had severe respira- tory illness, with about one-third resulting in death. The first case outside of China occurred in Malaysia and was reported in February 2014. The frightening feature of this virus is, that it does not belong to the group of highly pathogenic avian influenza viruses accord- ing to the structure of its surface glycoprotein hemagglutinin. This not only hampers proper surveillance in poultry but also chal- lenges the general concept of avian virus pathogenicity for humans (Liu et al., 2014). Fortunately also here no evidence of sustained http://dx.doi.org/10.1016/j.ijmm.2014.08.016 1438-4221/© 2014 Elsevier GmbH. All rights reserved.