Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro

Oxana V Denisova; Sandra Söderholm; Salla Virtanen; Carina Von Schantz; Dmitrii Bychkov; Elena Vashchinkina; Jens Desloovere; Janne Tynell; Niina Ikonen; Linda L Theisen; Tuula A Nyman; Sampsa Matikainen; Olli Kallioniemi; Ilkka Julkunen; Claude P Muller; Xavier Saelens; Vladislav V Verkhusha; Denis E Kainov

doi:10.1128/AAC.02798-13

Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro

Antimicrob Agents Chemother. 2014 Jul;58(7):3689-96. doi: 10.1128/AAC.02798-13. Epub 2014 Apr 21.

Authors

Oxana V Denisova¹, Sandra Söderholm², Salla Virtanen³, Carina Von Schantz¹, Dmitrii Bychkov¹, Elena Vashchinkina³, Jens Desloovere¹, Janne Tynell⁴, Niina Ikonen⁴, Linda L Theisen⁵, Tuula A Nyman⁶, Sampsa Matikainen⁷, Olli Kallioniemi¹, Ilkka Julkunen⁴, Claude P Muller⁵, Xavier Saelens⁸, Vladislav V Verkhusha⁹, Denis E Kainov¹⁰

Affiliations

¹ Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
² Institute of Biotechnology, University of Helsinki, Helsinki, Finland Finnish Institute of Occupational Health, University of Helsinki, Helsinki, Finland.
³ Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
⁴ Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare, University of Helsinki, Helsinki, Finland.
⁵ Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, Luxembourg, Luxembourg.
⁶ Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
⁷ Finnish Institute of Occupational Health, University of Helsinki, Helsinki, Finland.
⁸ VIB Inflammation Research Center and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
⁹ Department of Anatomy and Structural Biology and Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, USA.
¹⁰ Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland Department of Environmental Research, Siauliai University, Siauliai, Lithuania denis.kainov@helsinki.fi.

Abstract

The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus infection in vitro. In particular, at noncytotoxic concentrations, MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
Cytokines / metabolism
Heterocyclic Compounds, 3-Ring / pharmacology*
Host-Pathogen Interactions / drug effects
Humans
In Vitro Techniques
Influenza A Virus, H1N1 Subtype*
Influenza, Human / prevention & control*
Influenza, Human / virology
Molecular Sequence Data
Oncogene Protein v-akt / antagonists & inhibitors*
Phosphoproteins / metabolism
Protease Inhibitors / pharmacology*
RNA, Small Interfering / genetics
Transfection
Viral Plaque Assay

Substances

Cytokines
Heterocyclic Compounds, 3-Ring
MK 2206
Phosphoproteins
Protease Inhibitors
RNA, Small Interfering
Oncogene Protein v-akt

Associated data

GEO/GSE54293