[en] Advances in HIV therapy came from understanding its replication. Further progress toward "functional cure" -no therapy needed as found in Elite Controllers (EC)- may come from insights in pathogenesis and avoidance by EC. Here we show that all immune cells from HIV-infected persons are impaired in non-EC, but not in EC. Since HIV infects few cell types, these results suggest an additional mediator of pathogenesis. We identify that mediator as elevated pathogenic IFNα, controlled by EC likely by their preserved potent NK-cells and later by other killer cells. Since the earliest days of infection predict outcome genetic or chance events must be key to EC, and since we found no unique immune parameter at the onset, we suggest a chance infection with a lower HIV inoculum. These results offer an additional approach toward functional cure: a judicious targeting of IFNα for all non-EC patients.
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
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
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
Sajadi, Mohammad M; Global Virus Network, Baltimore, MD 21201, USA ; 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
Kottilil, Shyamasundaran; Global Virus Network, Baltimore, MD 21201, USA ; 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 ; 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
Gallo, Robert C; Global Virus Network, Baltimore, MD 21201, USA ; 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
