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IFNα induces CCR5 in CD4+ T-cells, causing its anti- HIV inefficiency and its subsequent pathogenic elevation, partially controlled by anti-HIV therapy.
Le Buanec, Hélène; Schiavon, Valérie; Merandet, Marineet al.
[en] Like EC, we find that ART-treated patients control serum IFNα concentration and show few immune cell alterations enabling a healthy but fragile medical status. However, treatment interruption leads to elevated IFNα reflecting virus production indicating that like EC, ART does not achieve a virological cure. The immune system becomes overwhelmed by multiple immune cell abnormalities as found in untreated patients. These are chiefly mediated by elevated IFNα inducing signaling checkpoints abnormalities, including PD1, in cytotoxic immune cells. Importantly, during acute infection, elevated IFNα correlated with HIV load and we found that IFNα enhances CCR5, the HIV coreceptor in CD4+ T-cells, impairing its anti-viral response and accounting for the pathogenic vicious cycle: HIV → IFNα ↗ → infected CD4+ T-cells ↗ →HIV ↗. This study opens immunotherapeutic perspectives showing the need to control IFNα in order to convert ART patients into EC.
Disciplines :
Immunology & infectious disease
Author, co-author :
Le Buanec, Hélène; Université de Paris, INSERM U976, HIPI Unit, Institut de Recherche Saint-Louis, F-75010 Paris, France
Schiavon, Valérie; Université de Paris, INSERM U976, HIPI Unit, Institut de Recherche Saint-Louis, F-75010 Paris, France
Merandet, Marine; Université de Paris, INSERM U976, HIPI Unit, Institut de Recherche Saint-Louis, F-75010 Paris, France
How-Kit, Alexandre; Laboratory for Genomics Foundation Jean Dausset-CEPH, Paris France
Song, Hongshuo; Institute of Human Virology, School of Medicine, University of Maryland, Baltimore MD, 21201, USA, Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA
Bergerat, David; Université de Paris, INSERM U976, HIPI Unit, Institut de Recherche Saint-Louis, F-75010 Paris, France
Bensussan, Armand ; Université de Paris, INSERM U976, HIPI Unit, Institut de Recherche Saint-Louis, F-75010 Paris, France
Bouaziz, Jean-David; Université de Paris, INSERM U976, HIPI Unit, Institut de Recherche Saint-Louis, F-75010 Paris, France ; Dermatology Department, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
Burny, Arsène ; Université de Liège - ULiège ; Global Virus Network, Baltimore, MD 21201, USA
Darcis, Gilles ; Centre Hospitalier Universitaire de Liège - CHU > > Service des maladies infectieuses - médecine interne
Sajadi, Mohammad M; Institute of Human Virology, School of Medicine, University of Maryland, Baltimore MD, 21201, USA, Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA ; Global Virus Network, Baltimore, MD 21201, USA
Kottilil, Shyamasundaran; Institute of Human Virology, School of Medicine, University of Maryland, Baltimore MD, 21201, USA, Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA ; Global Virus Network, Baltimore, MD 21201, USA ; University of Maryland School of Medicine, Baltimore, MD 21201, USA, Program in Oncology, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD 21201, USA
Zagury, Daniel; 21CBIO , Paris France
Gallo, Robert C; Institute of Human Virology, School of Medicine, University of Maryland, Baltimore MD, 21201, USA, Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA ; Global Virus Network, Baltimore, MD 21201, USA
IFNα induces CCR5 in CD4+ T-cells, causing its anti- HIV inefficiency and its subsequent pathogenic elevation, partially controlled by anti-HIV therapy.
