Kinome-Wide RNA Interference Screening Identifies Mitogen-Activated Protein Kinases and Phosphatidylinositol Metabolism as Key Factors for Rabies Virus Infection

Author:

Besson Benoit123ORCID,Kim Seonhee123,Kim Taehee4,Ko Yoonae4,Lee Sangchul4,Larrous Florence1ORCID,Song Jihwan5,Shum David4,Grailhe Regis4,Bourhy Hervé1

Affiliation:

1. Institut Pasteur, Unité Lyssavirus, épidémiologie et neuropathologie, Paris, France

2. Sorbonne Paris Cité, Cellule Pasteur, Université Paris Diderot, Paris, France

3. Technology Development Platform, Institut Pasteur Korea, Seongnam-si, Republic of Korea

4. Screening Discovery Platform, Institut Pasteur Korea, Seongnam-si, Republic of Korea

5. CHA Bio Complex, CHA Stem Cell Institute, Seongnam-si, Republic of Korea

Abstract

Rabies virus relies on cellular machinery for its replication while simultaneously evading the host immune response. Despite their importance, little is known about the key host factors required for rabies virus infection. Here, we focused on the human kinome, at the core of many cellular pathways, to unveil a new understanding of the rabies virus infectious cycle and to discover new potential therapeutic targets in a small interfering RNA screening. The mitogen-activated protein kinase pathway and phosphatidylinositol metabolism were identified as prominent factors involved in rabies virus infection, and those findings were further confirmed in human neurons. While bringing a new insight into rabies virus biology, we also provide a new list of host factors involved in rabies virus infection.

Funder

National Research Foundation of Korea

EC | Seventh Framework Programme

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

Reference64 articles.

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