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FHL1 is a major host factor for chikungunya virus infection

Author

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  • 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
    Hôpital Saint-Louis, APHP)

  • Marc Lecuit

    (Institut Pasteur, Inserm U1117, Biology of Infection Unit
    Necker-Enfants Malades University Hospital, APHP, Institut Imagine)

  • Ali Amara

    (Institut de Recherche Saint-Louis, Université de Paris, Hôpital Saint-Louis)

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.

Suggested Citation

  • Laurent Meertens & Mohamed Lamine Hafirassou & Thérèse Couderc & Lucie Bonnet-Madin & Vasiliya Kril & Beate M. Kümmerer & Athena Labeau & Alexis Brugier & Etienne Simon-Loriere & Julien Burlaud-Gailla, 2019. "FHL1 is a major host factor for chikungunya virus infection," Nature, Nature, vol. 574(7777), pages 259-263, October.
    • Handle: RePEc:nat:nature:v:574:y:2019:i:7777:d:10.1038_s41586-019-1578-4
    DOI: 10.1038/s41586-019-1578-4
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    Cited by:

    1. Vasiliya Kril & Michael Hons & Celine Amadori & Claire Zimberger & Laurine Couture & Yara Bouery & Julien Burlaud-Gaillard & Andrei Karpov & Denis Ptchelkine & Alexandra L. Thienel & Beate M. Kümmerer, 2024. "Alphavirus nsP3 organizes into tubular scaffolds essential for infection and the cytoplasmic granule architecture," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Wern Hann Ng & Xiang Liu & Zheng L. Ling & Camilla N. O. Santos & Lucas S. Magalhães & Andrew J. Kueh & Marco J. Herold & Adam Taylor & Joseph R. Freitas & Sandra Koit & Sainan Wang & Andrew R. Lloyd , 2023. "FHL1 promotes chikungunya and o’nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Ningning Wang & Andres Merits & Michael Veit & Laura Sandra Lello & Shuhan Kong & Houqi Jiao & Jie Chen & Yu Wang & Georgi Dobrikov & Félix A. Rey & Shuo Su, 2024. "LDL receptor in alphavirus entry: structural analysis and implications for antiviral therapy," Nature Communications, Nature, vol. 15(1), pages 1-7, December.

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