Macropinocytosis and Clathrin-Dependent Endocytosis Play Pivotal Roles for the Infectious Entry of Puumala Virus

Author:

Bauherr Sandy123,Larsberg Filip123,Petrich Annett123,Sperber Hannah Sabeth123,Klose-Grzelka Victoria123,Luckner Madlen1,Azab Walid4,Schade Matthias1ORCID,Höfer Chris Tina1,Lehmann Maik Joerg2,Witkowski Peter T.3,Krüger Detlev H.3,Herrmann Andreas15,Schwarzer Roland13ORCID

Affiliation:

1. Department of Molecular Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany

2. Department of Molecular Parasitology, Humboldt-Universität zu Berlin, Berlin, Germany

3. Institute of Virology, Charité Medical School, Berlin, Germany

4. Institut für Virologie, Zentrum für Infektionsmedizin, Freie Universität Berlin, Berlin, Germany

5. IRI Life Sciences, Humboldt-Universität zu Berlin, Berlin, Germany

Abstract

The family Hantaviridae comprises a diverse group of virus species and is considered an emerging global public health threat. Individual hantavirus species differ considerably in terms of their pathogenicity but also in their cell biology and host-pathogen interactions. In this study, we focused on the most prevalent pathogenic hantavirus in Europe, Puumala virus (PUUV), and investigated the entry and internalization of PUUV into mammalian cells. We show that both clathrin-mediated endocytosis and macropinocytosis are cellular pathways exploited by the virus to establish productive infections and demonstrate that pharmacological inhibition of macropinocytosis or a targeted knockdown using RNA interference significantly reduced viral infections. We also found indications of an increase of macropinocytic uptake upon PUUV infection, suggesting that the virus triggers specific cellular mechanisms in order to stimulate its own internalization, thus facilitating infection.

Funder

Infect-ERA

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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