Immuno-modulating properties of saliphenylhalamide, SNS-032, obatoclax, and gemcitabine

• Published in: Antiviral research 2016-02, Vol.126, p.69-80
• Main Authors: Söderholm, Sandra, Anastasina, Maria, Islam, Mohammad Majharul, Tynell, Janne, Poranen, Minna M., Bamford, Dennis H., Stenman, Jakob, Julkunen, Ilkka, Šaulienė, Ingrida, De Brabander, Jef K., Matikainen, Sampsa, Nyman, Tuula A., Saelens, Xavier, Kainov, Denis
• Format: Article
• Language: English
• Subjects: Amides - pharmacology; Antineoplastic Agents - pharmacology; Antiviral agents; Antiviral Agents - pharmacology; Cells, Cultured; Coinfection - drug therapy; Coinfection - virology; Cytokines - metabolism; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Humans; Immune responses; Immunity, Innate - drug effects; Immunologic Factors - pharmacology; Influenza A virus; Influenza A virus - drug effects; Influenza A virus - physiology; Influenza, Human - drug therapy; Influenza, Human - immunology; Influenza, Human - virology; Innate immunity; Interferon-alpha - drug effects; Interferon-alpha - immunology; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - immunology; Macrophages - virology; Oxazoles - pharmacology; Phosphoproteins - metabolism; Pyrroles - pharmacology; RNA, Viral - biosynthesis; Salicylates - pharmacology; Thiazoles - pharmacology; Virus Replication - drug effects; Virus Replication - physiology; Virus-host interaction
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2015.12.011

Influenza A viruses (IAVs) impact the public health and global economy by causing yearly epidemics and occasional pandemics. Several anti-IAV drugs are available and many are in development. However, the question remains which of these antiviral agents may allow activation of immune responses and protect patients against co- and re-infections. To answer to this question, we analysed immuno-modulating properties of the antivirals saliphenylhalamide (SaliPhe), SNS-032, obatoclax, and gemcitabine, and found that only gemcitabine did not impair immune responses in infected cells. It also allowed activation of innate immune responses in lipopolysaccharide (LPS)- and interferon alpha (IFNα)-stimulated macrophages. Moreover, immuno-mediators produced by gemcitabine-treated IAV-infected macrophages were able to prime immune responses in non-infected cells. Thus, we identified an antiviral agent which might be beneficial for treatment of patients with severe viral infections. •Several anti-IAV drugs are available and dozens are in development.•We developed method for analysis of immuno-modulating properties of anti-IAV agents.•Gemcitabine, but not SaliPhe, SNS-032 and obatoclax allowed activation of immune responses.•Gemcitabine may protect infected patients against co- and re-infections.