Project Title
Decoding Hantavirus Cardiopulmonary Syndrome: Unveiling Viral Mutations and Host Response
Partner Organisations
Internal ID
1241530
Principal Investigator
Type
applied research
Status
VIGENTE
Start Date
April 1, 2024
End Date
March 31, 2027
Organisations
Pontificia Universidad Católica de Chile
Fields of Science and Technology (OECD)
Medical and Health sciences

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    Item type:Publication,
    TGFβ links EBV to multisystem inflammatory syndrome in children
    (Springer Science and Business Media LLC, 2025-03-12)
    Carl Christoph Goetzke
    ;
    Mona Massoud
    ;
    Stefan Frischbutter
    ;
    Gabriela Maria Guerra
    ;
    Marta Ferreira-Gomes
    <jats:title>Abstract</jats:title> <jats:p>In a subset of children and adolescents, SARS-CoV-2 infection induces a severe acute hyperinflammatory shock<jats:sup>1</jats:sup> termed multisystem inflammatory syndrome in children (MIS-C) at four to eight weeks after infection. MIS-C is characterized by a specific T cell expansion<jats:sup>2</jats:sup> and systemic hyperinflammation<jats:sup>3</jats:sup>. The pathogenesis of MIS-C remains largely unknown. Here we show that acute MIS-C is characterized by impaired reactivation of virus-reactive memory T cells, which depends on increased serum levels of the cytokine TGFβ resembling those that occur during severe COVID-19 (refs. <jats:sup>4,5</jats:sup>). This functional impairment in T cell reactivity is accompanied by the presence of TGFβ-response signatures in T cells, B cells and monocytes along with reduced antigen-presentation capabilities of monocytes, and can be reversed by blocking TGFβ. Furthermore, T cell receptor repertoires of patients with MIS-C exhibit expansion of T cells expressing TCRVβ21.3, resembling Epstein–Barr virus (EBV)-reactive T cell clones capable of eliminating EBV-infected B cells. Additionally, serum TGFβ in patients with MIS-C can trigger EBV reactivation, which is reversible with TGFβ blockade. Clinically, the TGFβ-induced defect in T cell reactivity correlates with a higher EBV seroprevalence in patients with MIS-C compared with age-matched controls, along with the occurrence of EBV reactivation. Our findings establish a connection between SARS-CoV-2 infection and COVID-19 sequelae in children, in which impaired T cell cytotoxicity triggered by TGFβ overproduction leads to EBV reactivation and subsequent hyperinflammation.</jats:p>
    Scopus© Citations 4  2