Browsing by Author "Garcia-Sastre, Adolfo"

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    Autoantibodies against type I IFNs in patients with critical influenza pneumonia
    (2022) Zhang, Qian; Pizzorno, Andres; Miorin, Lisa; Bastard, Paul; Gervais, Adrian; Le Voyer, Tom; Bizien, Lucy; Manry, Jeremy; Rosain, Jeremie; Philippot, Quentin; Goavec, Kelian; Padey, Blandine; Cupic, Anastasija; Laurent, Emilie; Saker, Kahina; Vanker, Martti; Saerekannu, Karita; Garcia-Salum, Tamara; Ferres, Marcela; Le Corre, Nicole; Sanchez-Cespedes, Javier; Balsera-Manzanero, Maria; Carratala, Jordi; Retamar-Gentil, Pilar; Abelenda-Alonso, Gabriela; Valiente, Adoracion; Tiberghien, Pierre; Zins, Marie; Debette, Stephanie; Meyts, Isabelle; Haerynck, Filomeen; Castagnoli, Riccardo; Notarangelo, Luigi D.; Gonzalez-Granado, Luis I.; Dominguez-Pinilla, Nerea; Andreakos, Evangelos; Triantafyllia, Vasiliki; Rodriguez-Gallego, Carlos; Sole-Violan, Jordi; Ruiz-Hernandez, Jose Juan; Rodriguez de Castro, Felipe; Ferreres, Jose; Briones, Marisa; Wauters, Joost; Vanderbeke, Lore; Feys, Simon; Kuo, Chen-Yen; Lei, Wei-Te; Ku, Cheng-Lung; Tal, Galit; Etzioni, Amos; Hanna, Suhair; Fournet, Thomas; Casalegno, Jean-Sebastien; Queromes, Gregory; Argaud, Laurent; Javouhey, Etienne; Rosa-Calatrava, Manuel; Cordero, Elisa; Aydillo, Teresa; Medina, Rafael A.; Kisand, Kai; Puel, Anne; Jouanguy, Emmanuelle; Abel, Laurent; Cobat, Aurelie; Trouillet-Assant, Sophie; Garcia-Sastre, Adolfo; Casanova, Jean-Laurent
    In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine.
  • No Thumbnail Available
    Item
    TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation
    (2021) Ho, Jessica Sook Yuin; Mok, Bobo Wing-Yee; Campisi, Laura; Jordan, Tristan; Yildiz, Soner; Parameswaran, Sreeja; Wayman, Joseph A.; Gaudreault, Natasha N.; Meekins, David A.; Indran, Sabarish, V; Morozov, Igor; Trujillo, Jessie D.; Fstkchyan, Yesai S.; Rathnasinghe, Raveen; Zhu, Zeyu; Zheng, Simin; Zhao, Nan; White, Kris; Ray-Jones, Helen; Malysheva, Valeriya; Thiecke, Michiel J.; Lau, Siu-Ying; Liu, Honglian; Zhang, Anna Junxia; Lee, Andrew Chak-Yiu; Liu, Wen-Chun; Jangra, Sonia; Escalera, Alba; Aydillo, Teresa; Melo, Betsaida Salom; Guccione, Ernesto; Sebra, Robert; Shum, Elaine; Bakker, Jan; Kaufman, David A.; Moreira, Andre L.; Carossino, Mariano; Balasuriya, Udeni B. R.; Byun, Minji; Albrecht, Randy A.; Schotsaert, Michael; Garcia-Sastre, Adolfo; Chanda, Sumit K.; Miraldi, Emily R.; Jeyasekharan, Anand D.; TenOever, Benjamin R.; Spivakov, Mikhail; Weirauch, Matthew T.; Heinz, Sven; Chen, Honglin; Benner, Christopher; Richt, Juergen A.; Marazzi, Ivan
    The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro, and in vivo analyses, we report that topoisomerase 1 (TOP1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Therapeutic treatment with two doses of topotecan (TPT), an FDA-approved TOP1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as 4 days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of TOP1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing TOP1 inhibitors for severe coronavirus disease 2019 (COVID-19) in humans.
  • No Thumbnail Available
    Item
    Tracking the emergence of antigenic variants in influenza A virus epidemics in Brazil
    (2023) Pillai, Tara K.; Johnson, Katherine E.; Song, Timothy; Gregianini, Tatiana S.; Tatiana, G. Baccin; Wang, Guojun; Medina, Rafael A.; Van Bakel, Harm; Garcia-Sastre, Adolfo; Nelson, Martha, I; Ghedin, Elodie; Veiga, Ana B. G.
    Influenza A virus (IAV) circulation patterns differ in North America and South America, with influenza seasons often characterized by different subtypes and strains. However, South America is relatively undersampled considering the size of its population. To address this gap, we sequenced the complete genomes of 220 IAVs collected between 2009 and 2016 from hospitalized patients in southern Brazil. New genetic drift variants were introduced into southern Brazil each season from a global gene pool, including four H3N2 clades (3c, 3c2, 3c3, and 3c2a) and five H1N1pdm clades (clades 6, 7, 6b, 6c, and 6b1). In 2016, H1N1pdm viruses belonging to a new 6b1 clade caused a severe influenza epidemic in southern Brazil that arrived early and spread rapidly, peaking mid-autumn. Inhibition assays showed that the A/California/07/2009(H1N1) vaccine strain did not protect well against 6b1 viruses. Phylogenetically, most 6b1 sequences that circulated in southern Brazil belong to a single transmission cluster that rapidly diffused across susceptible populations, leading to the highest levels of influenza hospitalization and mortality seen since the 2009 pandemic. Continuous genomic surveillance is needed to monitor rapidly evolving IAVs for vaccine strain selection and understand their epidemiological impact in understudied regions.