FHL1 is a major host factor for chikungunya virus infection

Laurent Meertens (), Mohamed Lamine Hafirassou, Thérèse Couderc, Lucie Bonnet-Madin, Vasiliya Kril, Beate M. Kümmerer, Athena Labeau, Alexis Brugier, Etienne Simon-Loriere, Julien Burlaud-Gaillard, Cécile Doyen, Laura Pezzi, Thibaud Goupil, Sophia Rafasse, Pierre-Olivier Vidalain, Anne Bertrand-Legout, Lucie Gueneau, Raul Juntas-Morales, Rabah Ben Yaou, Gisèle Bonne, Xavier Lamballerie, Monsef Benkirane, Philippe Roingeard, Constance Delaugerre, Marc Lecuit and Ali Amara ()
Additional contact information
Laurent Meertens: Institut de Recherche Saint-Louis, Université de Paris, Hôpital Saint-Louis
Mohamed Lamine Hafirassou: Institut de Recherche Saint-Louis, Université de Paris, Hôpital Saint-Louis
Thérèse Couderc: Institut Pasteur, Inserm U1117, Biology of Infection Unit
Lucie Bonnet-Madin: Institut de Recherche Saint-Louis, Université de Paris, Hôpital Saint-Louis
Vasiliya Kril: Institut de Recherche Saint-Louis, Université de Paris, Hôpital Saint-Louis
Beate M. Kümmerer: University of Bonn Medical Centre
Athena Labeau: Institut de Recherche Saint-Louis, Université de Paris, Hôpital Saint-Louis
Alexis Brugier: Institut de Recherche Saint-Louis, Université de Paris, Hôpital Saint-Louis
Etienne Simon-Loriere: Institut Pasteur, G5 Evolutionary Genomics of RNA Viruses
Julien Burlaud-Gaillard: Université de Tours et CHRU de Tours
Cécile Doyen: CNRS-Université de Montpellier
Laura Pezzi: Unité des Virus Émergents, Aix-Marseille Univ, IRD190, Inserm 1207, EFS-IRBA
Thibaud Goupil: Institut Pasteur, Inserm U1117, Biology of Infection Unit
Sophia Rafasse: Institut Pasteur, Inserm U1117, Biology of Infection Unit
Pierre-Olivier Vidalain: Université Paris Descartes, CNRS UMR 8601
Anne Bertrand-Legout: Center of Research in Myology, Sorbonne Université, INSERM UMRS974
Lucie Gueneau: Center of Research in Myology, Sorbonne Université, INSERM UMRS974
Raul Juntas-Morales: Centre Hospitalier Universitaire de Montpellier
Rabah Ben Yaou: Center of Research in Myology, Sorbonne Université, INSERM UMRS974
Gisèle Bonne: Center of Research in Myology, Sorbonne Université, INSERM UMRS974
Xavier Lamballerie: Unité des Virus Émergents, Aix-Marseille Univ, IRD190, Inserm 1207, EFS-IRBA
Monsef Benkirane: CNRS-Université de Montpellier
Philippe Roingeard: Université de Tours et CHRU de Tours
Constance Delaugerre: Institut de Recherche Saint-Louis, Université de Paris, Hôpital Saint-Louis
Marc Lecuit: Institut Pasteur, Inserm U1117, Biology of Infection Unit
Ali Amara: Institut de Recherche Saint-Louis, Université de Paris, Hôpital Saint-Louis

Nature, 2019, vol. 574, issue 7777, 259-263

Abstract: Abstract Chikungunya virus (CHIKV) is a re-emerging alphavirus that is transmitted to humans by mosquito bites and causes musculoskeletal and joint pain1,2. Despite intensive investigations, the human cellular factors that are critical for CHIKV infection remain unknown, hampering the understanding of viral pathogenesis and the development of anti-CHIKV therapies. Here we identified the four-and-a-half LIM domain protein 1 (FHL1)3 as a host factor that is required for CHIKV permissiveness and pathogenesis in humans and mice. Ablation of FHL1 expression results in the inhibition of infection by several CHIKV strains and o’nyong-nyong virus, but not by other alphaviruses and flaviviruses. Conversely, expression of FHL1 promotes CHIKV infection in cells that do not normally express it. FHL1 interacts directly with the hypervariable domain of the nsP3 protein of CHIKV and is essential for the replication of viral RNA. FHL1 is highly expressed in CHIKV-target cells and is particularly abundant in muscles3,4. Dermal fibroblasts and muscle cells derived from patients with Emery–Dreifuss muscular dystrophy that lack functional FHL15 are resistant to CHIKV infection. Furthermore, CHIKV infection is undetectable in Fhl1-knockout mice. Overall, this study shows that FHL1 is a key factor expressed by the host that enables CHIKV infection and identifies the interaction between nsP3 and FHL1 as a promising target for the development of anti-CHIKV therapies.

Date: 2019
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DOI: 10.1038/s41586-019-1578-4

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